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Journal of Mammary Gland Biology and Neoplasia

Erschienen in:

01.07.2014

Mammary Gland Involution as an Immunotherapeutic Target for Postpartum Breast Cancer

verfasst von: Jaime Fornetti, Holly A. Martinson, Courtney B. Betts, Traci R. Lyons, Sonali Jindal, Qiuchen Guo, Lisa M. Coussens, Virginia F. Borges, Pepper Schedin

Erschienen in: Journal of Mammary Gland Biology and Neoplasia | Ausgabe 2/2014

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Abstract

Postpartum mammary gland involution has been identified as tumor-promotional and is proposed to contribute to the increased rates of metastasis and poor survival observed in postpartum breast cancer patients. In rodent models, the involuting mammary gland microenvironment is sufficient to induce enhanced tumor cell growth, local invasion, and metastasis. Postpartum involution shares many attributes with wound healing, including upregulation of genes involved in immune responsiveness and infiltration of tissue by immune cells. In rodent models, treatment with non-steroidal anti-inflammatory drugs (NSAIDs) ameliorates the tumor-promotional effects of involution, consistent with the immune milieu of the involuting gland contributing to tumor promotion. Currently, immunotherapy is being investigated as a means of breast cancer treatment with the purpose of identifying ways to enhance anti-tumor immune responses. Here we review evidence for postpartum mammary gland involution being a uniquely defined ‘hot-spot’ of pro-tumorigenic immune cell infiltration, and propose that immunotherapy should be explored for prevention and treatment of breast cancers that arise in this environment.

Sasmono RT, Oceandy D, Pollard JW, Tong W, Pavli P, Wainwright BJ, et al. A macrophage colony-stimulating factor receptor-green fluorescent protein transgene is expressed throughout the mononuclear phagocyte system of the mouse. Blood. 2003;101(3):1155–63. doi:10.1182/blood-2002-02-0569.PubMed

Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature. 2013;496(7446):445–55. doi:10.1038/nature12034.PubMedCentralPubMed

Gouon-Evans V, Rothenberg ME, Pollard JW. Postnatal mammary gland development requires macrophages and eosinophils. Development. 2000;127(11):2269–82.PubMed

Van Nguyen A, Pollard JW. Colony stimulating factor-1 is required to recruit macrophages into the mammary gland to facilitate mammary ductal outgrowth. Dev Biol. 2002;247(1):11–25. doi:10.1006/dbio.2002.0669.PubMed

Chua AC, Hodson LJ, Moldenhauer LM, Robertson SA, Ingman WV. Dual roles for macrophages in ovarian cycle-associated development and remodelling of the mammary gland epithelium. Development. 2010;137(24):4229–38. doi:10.1242/dev.059261.PubMed

Hodson LJ, Chua AC, Evdokiou A, Robertson SA, Ingman WV. Macrophage phenotype in the mammary gland fluctuates over the course of the estrous cycle and is regulated by ovarian steroid hormones. Biol Reprod. 2013;89(3):6. doi:10.1095/biolreprod.113.109561.

Pollard JW, Hennighausen L. Colony stimulating factor 1 is required for mammary gland development during pregnancy. Proc Natl Acad Sci U S A. 1994;91(20):9312–6.PubMedCentralPubMed

O’Brien J, Martinson H, Durand-Rougely C, Schedin P. Macrophages are crucial for epithelial cell death and adipocyte repopulation during mammary gland involution. Development. 2012;139(2):269–75. doi:10.1242/dev.071696.PubMed

Lilla JN, Joshi RV, Craik CS, Werb Z. Active plasma kallikrein localizes to mast cells and regulates epithelial cell apoptosis, adipocyte differentiation, and stromal remodeling during mammary gland involution. J Biol Chem. 2009;284(20):13792–803. doi:10.1074/jbc.M900508200.PubMedCentralPubMed

10.

Lambe M, Hsieh C, Trichopoulos D, Ekbom A, Pavia M, Adami HO. Transient increase in the risk of breast cancer after giving birth. N Engl J Med. 1994;331(1):5–9. doi:10.1056/NEJM199407073310102.PubMed

11.

Liu Q, Wuu J, Lambe M, Hsieh SF, Ekbom A, Hsieh CC. Transient increase in breast cancer risk after giving birth: postpartum period with the highest risk (Sweden). Cancer Causes Control. 2002;13(4):299–305.PubMed

12.

Schedin P. Pregnancy-associated breast cancer and metastasis. Nat Rev Cancer. 2006;6(4):281–91. doi:10.1038/nrc1839.PubMed

13.

Albrektsen G, Heuch I, Hansen S, Kvale G. Breast cancer risk by age at birth, time since birth and time intervals between births: exploring interaction effects. Br J Cancer. 2005;92(1):167–75. doi:10.1038/sj.bjc.6602302.PubMedCentralPubMed

14.

Chie WC, Hsieh C, Newcomb PA, Longnecker MP, Mittendorf R, Greenberg ER, et al. Age at any full-term pregnancy and breast cancer risk. Am J Epidemiol. 2000;151(7):715–22.PubMed

15.

Albrektsen G, Heuch I, Kvale G. The short-term and long-term effect of a pregnancy on breast cancer risk: a prospective study of 802,457 parous Norwegian women. Br J Cancer. 1995;72(2):480–4.PubMedCentralPubMed

16.

Leon DA, Carpenter LM, Broeders MJ, Gunnarskog J, Murphy MF. Breast cancer in Swedish women before age 50: evidence of a dual effect of completed pregnancy. Cancer Causes Control. 1995;6(4):283–91.PubMed

17.

Janerich DT, Hoff MB. Evidence for a crossover in breast cancer risk factors. Am J Epidemiol. 1982;116(5):737–42.PubMed

18.

Lyons TR, Schedin PJ, Borges VF. Pregnancy and breast cancer: when they collide. J Mammary Gland Biol Neoplasia. 2009;14(2):87–98. doi:10.1007/s10911-009-9119-7.PubMedCentralPubMed

19.

Stensheim H, Moller B, van Dijk T, Fossa SD. Cause-specific survival for women diagnosed with cancer during pregnancy or lactation: a registry-based cohort study. J Clin Oncol. 2009;27(1):45–51. doi:10.1200/JCO.2008.17.4110.PubMed

20.

Johansson AL, Andersson TM, Hsieh CC, Cnattingius S, Lambe M. Increased mortality in women with breast cancer detected during pregnancy and different periods postpartum. Cancer Epidemiol Biomarkers Prev. 2011;20(9):1865–72. doi:10.1158/1055-9965.EPI-11-0515.PubMed

21.

Callihan EB, Gao D, Jindal S, Lyons TR, Manthey E, Edgerton S, et al. Postpartum diagnosis demonstrates a high risk for metastasis and merits an expanded definition of pregnancy-associated breast cancer. Breast Cancer Res Treat. 2013;138(2):549–59. doi:10.1007/s10549-013-2437-x.PubMedCentralPubMed

22.

Bonnier P, Romain S, Dilhuydy JM, Bonichon F, Julien JP, Charpin C, et al. Influence of pregnancy on the outcome of breast cancer: a case–control study. Societe Francaise de senologie et de pathologie mammaire study group. Int J Cancer. 1997;72(5):720–7. doi:10.1002/(SICI)1097-0215(19970904)72:5<720::AID-IJC3>3.0.CO;2-U.PubMed

23.

Daling JR, Malone KE, Doody DR, Anderson BO, Porter PL. The relation of reproductive factors to mortality from breast cancer. Cancer Epidemiol Biomarkers Prev. 2002;11(3):235–41.PubMed

24.

Olson SH, Zauber AG, Tang J, Harlap S. Relation of time since last birth and parity to survival of young women with breast cancer. Epidemiology. 1998;9(6):669–71.

25.

O’Brien J, Schedin P. Macrophages in breast cancer: do involution macrophages account for the poor prognosis of pregnancy-associated breast cancer? J Mammary Gland Biol Neoplasia. 2009;14(2):145–57. doi:10.1007/s10911-009-9118-8.

26.

Jindal S, Gao D, Bell P, Albrektsen G, Edgerton S, Ambrosone C, et al. Postpartum breast involution reveals regression of secretory lobules mediated by tissue-remodeling. Breast Cancer Res. 2014;16(2):R31.PubMedCentralPubMed

27.

Lund LR, Romer J, Thomasset N, Solberg H, Pyke C, Bissell MJ, et al. Two distinct phases of apoptosis in mammary gland involution: proteinase-independent and -dependent pathways. Development. 1996;122(1):181–93.PubMedCentralPubMed

28.

McDaniel SM, Rumer KK, Biroc SL, Metz RP, Singh M, Porter W, et al. Remodeling of the mammary microenvironment after lactation promotes breast tumor cell metastasis. Am J Pathol. 2006;168(2):608–20. doi:10.2353/ajpath.2006.050677.PubMedCentralPubMed

29.

Stein T, Morris J, Davies C, Weber-Hall S, Duffy M-A, Heath V, et al. Involution of the mouse mammary gland is associated with an immune cascade and an acute-phase response, involving LBP, CD14 and STAT3. Breast Cancer Res. 2004;6(2):R75–91.PubMedCentralPubMed

30.

Walker NI, Bennett RE, Kerr JF. Cell death by apoptosis during involution of the lactating breast in mice and rats. Am J Anat. 1989;185(1):19–32. doi:10.1002/aja.1001850104.PubMed

31.

Li M, Liu X, Robinson G, Bar-Peled U, Wagner KU, Young WS, et al. Mammary-derived signals activate programmed cell death during the first stage of mammary gland involution. Proc Natl Acad Sci U S A. 1997;94(7):3425–30.PubMedCentralPubMed

32.

Marti A, Feng Z, Altermatt HJ, Jaggi R. Milk accumulation triggers apoptosis of mammary epithelial cells. Eur J Cell Biol. 1997;73(2):158–65.PubMed

33.

Kreuzaler PA, Staniszewska AD, Li W, Omidvar N, Kedjouar B, Turkson J, et al. Stat3 controls lysosomal-mediated cell death in vivo. Nat Cell Biol. 2011;13(3):303–9. doi:10.1038/ncb2171.PubMed

34.

Dickson SR, Warburton MJ. Enhanced synthesis of gelatinase and stromelysin by myoepithelial cells during involution of the rat mammary gland. J Histochem Cytochem. 1992;40(5):697–703.PubMed

35.

Lefebvre O, Wolf C, Limacher JM, Hutin P, Wendling C, LeMeur M, et al. The breast cancer-associated stromelysin-3 gene is expressed during mouse mammary gland apoptosis. J Cell Biol. 1992;119(4):997–1002.PubMed

36.

Strange R, Li F, Saurer S, Burkhardt A, Friis RR. Apoptotic cell death and tissue remodelling during mouse mammary gland involution. Development. 1992;115(1):49–58.PubMed

37.

Talhouk RS, Bissell MJ, Werb Z. Coordinated expression of extracellular matrix-degrading proteinases and their inhibitors regulates mammary epithelial function during involution. J Cell Biol. 1992;118(5):1271–82.PubMed

38.

Clarkson R, Wayland M, Lee J, Freeman T, Watson C. Gene expression profiling of mammary gland development reveals putative roles for death receptors and immune mediators in post-lactational regression. Breast Cancer Res. 2004;6(2):R92–109.PubMedCentralPubMed

39.

O’Brien J, Lyons T, Monks J, Lucia MS, Wilson RS, Hines L, et al. Alternatively activated macrophages and collagen remodeling characterize the postpartum involuting mammary gland across species. Am J Pathol. 2010;176(3):1241–55. doi:10.2353/ajpath.2010.090735.PubMedCentralPubMed

40.

Schedin P, Mitrenga T, McDaniel S, Kaeck M. Mammary ECM composition and function are altered by reproductive state. Mol Carcinog. 2004;41(4):207–20. doi:10.1002/mc.20058.PubMed

41.

Schedin P, O’Brien J, Rudolph M, Stein T, Borges V. Microenvironment of the involuting mammary gland mediates mammary cancer progression. J Mammary Gland Biol Neoplasia. 2007;12(1):71–82. doi:10.1007/s10911-007-9039-3.PubMed

42.

Schedin P, Strange R, Mitrenga T, Wolfe P, Kaeck M. Fibronectin fragments induce MMP activity in mouse mammary epithelial cells: evidence for a role in mammary tissue remodeling. J Cell Sci. 2000;113(Pt 5):795–806.PubMed

43.

Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860–7. doi:10.1038/nature01322.PubMedCentralPubMed

44.

Fornetti J, Jindal S, Middleton KA, Borges VF, Schedin P. Physiological COX-2 expression in breast epithelium associates with COX-2 levels in ductal carcinoma in situ and invasive breast cancer in young women. Am J Pathol. 2014;184(4):1219–29. doi:10.1016/j.ajpath.2013.12.026.PubMed

45.

Gupta PB, Proia D, Cingoz O, Weremowicz J, Naber SP, Weinberg RA, et al. Systemic stromal effects of estrogen promote the growth of estrogen receptor–negative cancers. Cancer Res. 2007;67(5):2062–71. doi:10.1158/0008-5472.can-06-3895.PubMed

46.

Fornetti J, Martinson H, Borges V, Schedin P. Emerging targets for the prevention of pregnancy-associated breast cancer. Cell Cycle. 2012;11(4):639–40. doi:10.4161/cc.11.4.19358.PubMedCentralPubMed

47.

Stein T, Salomonis N, Nuyten DS, van de Vijver MJ, Gusterson BA. A mouse mammary gland involution mRNA signature identifies biological pathways potentially associated with breast cancer metastasis. J Mammary Gland Biol Neoplasia. 2009;14(2):99–116. doi:10.1007/s10911-009-9120-1.PubMed

48.

Monks J, Smith-Steinhart C, Kruk ER, Fadok VA, Henson PM. Epithelial cells remove apoptotic epithelial cells during post-lactation involution of the mouse mammary gland. Biol Reprod. 2008;78(4):586–94. doi:10.1095/biolreprod.107.065045.PubMed

49.

Hughes K, Wickenden JA, Allen JE, Watson CJ. Conditional deletion of Stat3 in mammary epithelium impairs the acute phase response and modulates immune cell numbers during post-lactational regression. J Pathol. 2012;227(1):106–17. doi:10.1002/path.3961.PubMedCentralPubMed

50.

Ramirez RA, Lee A, Schedin P, Russell JS, Masso-Welch PA. Alterations in mast cell frequency and relationship to angiogenesis in the rat mammary gland during windows of physiologic tissue remodeling. Dev Dyn. 2012;241(5):890–900. doi:10.1002/dvdy.23778.PubMedCentralPubMed

51.

Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004;25(12):677–86.PubMed

52.

Sica A, Schioppa T, Mantovani A, Allavena P. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer. 2006;42(6):717–27. doi:10.1016/j.ejca.2006.01.003.PubMed

53.

Sica A, Larghi P, Mancino A, Rubino L, Porta C, Totaro MG, et al. Macrophage polarization in tumour progression. Semin Cancer Biol. 2008;18(5):349–55.PubMed

54.

Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008;8(12):958–69.PubMedCentralPubMed

55.

Mantovani A, Sozzani S, Locati M, Allavena P, Sica A. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002;23(11):549–55.

56.

Sohn BH, Moon HB, Kim TY, Kang HS, Bae YS, Lee KK, et al. Interleukin-10 up-regulates tumour-necrosis-factor-alpha-related apoptosis-inducing ligand (TRAIL) gene expression in mammary epithelial cells at the involution stage. Biochem J. 2001;360(Pt 1):31–8.PubMedCentralPubMed

57.

Chang SH, Liu CH, Conway R, Han DK, Nithipatikom K, Trifan OC, et al. Role of prostaglandin E2-dependent angiogenic switch in cyclooxygenase 2-induced breast cancer progression. Proc Natl Acad Sci U S A. 2004;101(2):591–6. doi:10.1073/pnas.2535911100.PubMedCentralPubMed

58.

Hu M, Peluffo G, Chen H, Gelman R, Schnitt S, Polyak K. Role of COX-2 in epithelial-stromal cell interactions and progression of ductal carcinoma in situ of the breast. Proc Natl Acad Sci U S A. 2009;106((9):3372–7. doi:10.1073/pnas.0813306106.

59.

Karavitis J, Hix LM, Shi YH, Schultz RF, Khazaie K, Zhang M. Regulation of COX2 expression in mouse mammary tumor cells controls bone metastasis and PGE2-induction of regulatory T cell migration. PLoS One. 2012;7(9):e46342. doi:10.1371/journal.pone.0046342.PubMedCentralPubMed

60.

Larkins T, Nowell M, Singh S, Sanford G. Inhibition of cyclooxygenase-2 decreases breast cancer cell motility, invasion and matrix metalloproteinase expression. BMC Cancer. 2006;6(1):181.PubMedCentralPubMed

61.

Liu CH, Chang S-H, Narko K, Trifan OC, Wu M-T, Smith E, et al. Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J Biol Chem. 2001;276(21):18563–9. doi:10.1074/jbc.M010787200.PubMed

62.

Lyons TR, O’Brien J, Borges VF, Conklin MW, Keely PJ, Eliceiri KW et al. Postpartum mammary gland involution drives progression of ductal carcinoma in situ through collagen and COX-2. Nat Med. 2011;17(9):1109–15. doi:http://www.nature.com/nm/journal/v17/n9/abs/nm.2416.html#supplementary-information.

63.

Sinha P, Clements VK, Fulton AM, Ostrand-Rosenberg S. Prostaglandin E2 promotes tumor progression by inducing myeloid-derived suppressor cells. Cancer Res. 2007;67(9):4507–13. doi:10.1158/0008-5472.CAN-06-4174.PubMed

64.

Xiang X, Poliakov A, Liu C, Liu Y, Deng ZB, Wang J, et al. Induction of myeloid-derived suppressor cells by tumor exosomes. Int J Cancer. 2009;124(11):2621–33. doi:10.1002/ijc.24249.PubMedCentralPubMed

65.

Chen EP, Smyth EM. COX-2 and PGE2-dependent immunomodulation in breast cancer. Prostaglandins Other Lipid Mediat. 2011;96(1–4):14–20. doi:10.1016/j.prostaglandins.2011.08.005.PubMedCentralPubMed

66.

O’Brien J, Hansen K, Barkan D, Green J, Schedin P. Non-steroidal anti-inflammatory drugs target the pro-tumorigenic extracellular matrix of the postpartum mammary gland. Int J Dev Biol. 2011;55(7–9):745–55. doi:10.1387/ijdb.113379jo.PubMed

67.

Sandahl M, Hunter DM, Strunk KE, Earp HS, Cook RS. Epithelial cell-directed efferocytosis in the post-partum mammary gland is necessary for tissue homeostasis and future lactation. BMC Dev Biol. 2010;10:122. doi:10.1186/1471-213X-10-122.PubMedCentralPubMed

68.

Fadok VA, Bratton DL, Konowal A, Freed OW. Macrophages That Have Ingested Apoptotic Cells In Vitro Inhibit Proinflammatory Cytokine Production Through Autocrine/Paracrine Mechanisms Involving TGF-beta, PGE2, and PAF. J Clin Invest. 1998;101.

69.

Chung EY, Liu J, Homma Y, Zhang Y, Brendolan A, Saggese M, et al. Interleukin-10 expression in macrophages during phagocytosis of apoptotic cells is mediated by homeodomain proteins Pbx1 and prep-1. Immunity. 2007;27(6):952–64. doi:10.1016/j.immuni.2007.11.014.PubMedCentralPubMed

70.

Brecht K, Weigert A, Hu J, Popp R, Fisslthaler B, Korff T, et al. Macrophages programmed by apoptotic cells promote angiogenesis via prostaglandin E2. FASEB J. 2011;25(7):2408–17. doi:10.1096/fj.10-179473.PubMed

71.

Monks J, Rosner D, Geske FJ, Lehman L, Hanson L, Neville MC, et al. Epithelial cells as phagocytes: apoptotic epithelial cells are engulfed by mammary alveolar epithelial cells and repress inflammatory mediator release. Cell Death Differ. 2005;12(2):107–14. doi:10.1038/sj.cdd.4401517.PubMed

72.

Chapman RS, Lourenco P, Tonner E, Flint D, Selbert S, Takeda K, et al. The role of Stat3 in apoptosis and mammary gland involution. Conditional deletion of Stat3. Adv Exp Med Biol. 2000;480:129–38.PubMed

73.

Golpon HA, Fadok VA, Taraseviciene-Stewart L, Scerbavicius R, Sauer C, Welte T, et al. Life after corpse engulfment: phagocytosis of apoptotic cells leads to VEGF secretion and cell growth. FASEB J. 2004;18(14):1716–8. doi:10.1096/fj.04-1853fje.PubMed

74.

Gregory CD, Pound JD. Cell death in the neighbourhood: direct microenvironmental effects of apoptosis in normal and neoplastic tissues. J Pathol. 2011;223(2):177–94. doi:10.1002/path.2792.PubMed

75.

Somersan S. Tethering and tickling: a new role for the phosphatidylserine receptor. J Cell Biol. 2001;155(4):501–4. doi:10.1083/jcb.200110066.PubMedCentralPubMed

76.

Lauber K, Bohn E, Kröber SM, Xiao Y-j, Blumenthal SG, Lindemann RK, et al. Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell. 2003;113(6):717–30. doi:10.1016/s0092-8674(03)00422-7.PubMed

77.

Elliott MR, Chekeni FB, Trampont PC, Lazarowski ER, Kadl A, Walk SF, et al. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature. 2009;461(7261):282–6. doi:10.1038/nature08296.PubMedCentralPubMed

78.

Yamaguchi H, Maruyama T, Urade Y, Nagata S. Immunosuppression via adenosine receptor activation by adenosine monophosphate released from apoptotic cells. eLife. 2014. doi:10.7554/eLife.02172.001 10.7554/eLife.02172.002.

79.

Chen W, Frank ME, Jin W, Wahl SM. TGF-beta Released by Apoptotic T Cells Contributes to an Immunosuppressive Milieu. Immunity. 2001;14.

80.

Li F, Huang Q, Chen J, Peng Y, Roop DR, Bedford JS, et al. Apoptotic cells activate the “phoenix rising” pathway to promote wound healing and tissue regeneration. Sci Signal. 2010;3(110):ra13. doi:10.1126/scisignal.2000634.PubMedCentralPubMed

81.

Yañez R, Oviedo A, Aldea M, Bueren JA, Lamana ML. Prostaglandin E2 plays a key role in the immunosuppressive properties of adipose and bone marrow tissue-derived mesenchymal stromal cells. Exp Cell Res. 2010;316(19):3109–23. doi:10.1016/j.yexcr.2010.08.008.PubMed

82.

O’Brien JH, Vanderlinden LA, Schedin PJ, Hansen KC. Rat mammary extracellular matrix composition and response to ibuprofen treatment during postpartum involution by differential GeLC-MS/MS analysis. J Proteome Res. 2012;11(10):4894–905. doi:10.1021/pr3003744.PubMed

83.

Morwood SR, Nicholson LB. Modulation of the immune response by extracellular matrix proteins. Arch Immunol Ther Exp (Warsz). 2006;54(6):367–74. doi:10.1007/s00005-006-0043-x.

84.

Sorokin L. The impact of the extracellular matrix on inflammation. Nat Rev Immunol. 2010;0((0)):712–23. doi:10.1038/nri2852.

85.

Laskin DL, Soltys RA, Berg RA, Riley DJ. Activation of alveolar macrophages by native and synthetic collagen-like polypeptides. Am J Respir Cell Mol Biol. 1994;10(1):58–64. doi:10.1165/ajrcmb.10.1.8292381.PubMed

86.

Mydel P, Shipley JM, Adair-Kirk TL, Kelley DG, Broekelmann TJ, Mecham RP, et al. Neutrophil elastase cleaves laminin-332 (laminin-5) generating peptides that are chemotactic for neutrophils. J Biol Chem. 2008;283(15):9513–22. doi:10.1074/jbc.M706239200.PubMedCentralPubMed

87.

Kaplan G. In vitro differentiation of human monocytes. Monocytes cultured on glass are cytotoxic to tumor cells but monocytes cultured on collagen are not. J Exp Med. 1983;157(6):2061–72.PubMed

88.

Hauzenberger D, Olivier P, Gundersen D, Ruegg C. Tenascin-C inhibits beta1 integrin-dependent T lymphocyte adhesion to fibronectin through the binding of its fnIII 1–5 repeats to fibronectin. Eur J Immunol. 1999;29(5):1435–47. doi:10.1002/(SICI)1521-4141(199905)29:05<1435::AID-IMMU1435>3.0.CO;2-N.PubMed

89.

Hemesath TJ, Marton LS, Stefansson K. Inhibition of T cell activation by the extracellular matrix protein tenascin. J Immunol. 1994;152(11):5199–207.PubMed

90.

Hibino S, Kato K, Kudoh S, Yagita H, Okumura K. Tenascin suppresses CD3-mediated T cell activation. Biochem Biophys Res Commun. 1998;250(1):119–24. doi:10.1006/bbrc.1998.9258.PubMed

91.

Puente Navazo MD, Valmori D, Ruegg C. The alternatively spliced domain TnFnIII A1A2 of the extracellular matrix protein tenascin-C suppresses activation-induced T lymphocyte proliferation and cytokine production. J Immunol. 2001;167(11):6431–40.PubMed

92.

Ruegg CR, Chiquet-Ehrismann R, Alkan SS. Tenascin, an extracellular matrix protein, exerts immunomodulatory activities. Proc Natl Acad Sci U S A. 1989;86(19):7437–41.PubMedCentralPubMed

93.

Maller O, Martinson H, Schedin P. Extracellular matrix composition reveals complex and dynamic stromal-epithelial interactions in the mammary gland. J Mammary Gland Biol Neoplasia. 2010;15(3):301–18. doi:10.1007/s10911-010-9189-6.PubMed

94.

Korpos E, Wu C, Sorokin L. Multiple roles of the extracellular matrix in inflammation. Curr Pharm Des. 2009;15(12):1349–57.PubMed

95.

Vaday GG, Lider O. Extracellular matrix moieties, cytokines, and enzymes: dynamic effects on immune cell behavior and inflammation. J Leukoc Biol. 2000;67(2):149–59.PubMed

96.

Lortat-Jacob H, Garrone P, Banchereau J, Grimaud JA. Human interleukin 4 is a glycosaminoglycan-binding protein. Cytokine. 1997;9(2):101–5. doi:10.1006/cyto.1996.0142.PubMed

97.

Schedin P, Mitrenga T, Kaeck M. Estrous cycle regulation of mammary epithelial cell proliferation, differentiation, and death in the Sprague–Dawley Rat: a model for investigating the role of estrous cycling in mammary carcinogenesis. J Mammary Gland Biol Neoplasia. 2000;5(2):211–25. doi:10.1023/a:1026447506666.PubMed

98.

Hinz B. Formation and function of the myofibroblast during tissue repair. J Investig Dermatol. 2007;127(3):526–37. doi:10.1038/sj.jid.5700613.PubMed

99.

Annes JP, Munger JS, Rifkin DB. Making sense of latent TGFbeta activation. J Cell Sci. 2003;116(Pt 2):217–24.PubMed

100.

Flanders KC, Wakefield LM. Transforming growth factor-(beta)s and mammary gland involution; functional roles and implications for cancer progression. J Mammary Gland Biol Neoplasia. 2009;14(2):131–44. doi:10.1007/s10911-009-9122-z.PubMedCentralPubMed

101.

Ahmadzadeh M, Rosenberg SA. TGF-beta 1 attenuates the acquisition and expression of effector function by tumor antigen-specific human memory CD8 T cells. J Immunol. 2005;174(9):5215–23.PubMedCentralPubMed

102.

Kitamura M. Identification of an inhibitor targeting macrophage production of monocyte chemoattractant protein-1 as TGF-beta 1. J Immunol. 1997;159(3):1404–11.PubMed

103.

Chen JJ, Sun Y, Nabel GJ. Regulation of the proinflammatory effects of Fas ligand (CD95L). Science. 1998;282(5394):1714–7.PubMed

104.

Ghiringhelli F, Menard C, Terme M, Flament C, Taieb J, Chaput N, et al. CD4 + CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner. J Exp Med. 2005;202(8):1075–85. doi:10.1084/jem.20051511.PubMedCentralPubMed

105.

Geissmann F, Revy P, Regnault A, Lepelletier Y, Dy M, Brousse N, et al. TGF-beta 1 prevents the noncognate maturation of human dendritic Langerhans cells. J Immunol. 1999;162(8):4567–75.PubMed

106.

Wahl SM, Chen W. Transforming growth factor-beta-induced regulatory T cells referee inflammatory and autoimmune diseases. Arthritis Res Ther. 2005;7(2):62–8. doi:10.1186/ar1504.PubMedCentralPubMed

107.

O’Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell. 1997;88(2):277–85.PubMed

108.

Hamano Y, Zeisberg M, Sugimoto H, Lively JC, Maeshima Y, Yang C, et al. Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphaV beta3 integrin. Cancer Cell. 2003;3(6):589–601.PubMedCentralPubMed

109.

Adair-Kirk TL, Senior RM. Fragments of extracellular matrix as mediators of inflammation. Int J Biochem Cell Biol. 2008;40(6–7):1101–10. doi:10.1016/j.biocel.2007.12.005.PubMedCentralPubMed

110.

Brown EJ. The role of extracellular matrix proteins in the control of phagocytosis. J Leukoc Biol. 1986;39(5):579–91.PubMed

111.

Yang KD, Augustine NH, Shaio MF, Bohnsack JF, Hill HR. Effects of fibronectin on actin organization and respiratory burst activity in neutrophils, monocytes, and macrophages. J Cell Physiol. 1994;158(2):347–53. doi:10.1002/jcp.1041580217.PubMed

112.

Beezhold DH, Personius C. Fibronectin fragments stimulate tumor necrosis factor secretion by human monocytes. J Leukoc Biol. 1992;51(1):59–64.PubMed

113.

Marom B, Rahat MA, Lahat N, Weiss-Cerem L, Kinarty A, Bitterman H. Native and fragmented fibronectin oppositely modulate monocyte secretion of MMP-9. J Leukoc Biol. 2007;81(6):1466–76. doi:10.1189/jlb.0506328.PubMed

114.

Adair-Kirk TL, Atkinson JJ, Broekelmann TJ, Doi M, Tryggvason K, Miner JH, et al. A site on laminin alpha 5, AQARSAASKVKVSMKF, induces inflammatory cell production of matrix metalloproteinase-9 and chemotaxis. J Immunol. 2003;171(1):398–406.PubMed

115.

Adair-Kirk TL, Atkinson JJ, Kelley DG, Arch RH, Miner JH, Senior RM. A chemotactic peptide from laminin alpha 5 functions as a regulator of inflammatory immune responses via TNF alpha-mediated signaling. J Immunol. 2005;174(3):1621–9.PubMed

116.

McCready J, Arendt LM, Glover E, Iyer V, Briendel JL, Lyle SR, et al. Pregnancy-associated breast cancers are driven by differences in adipose stromal cells present during lactation. Breast Cancer Res. 2014;16(1):R2. doi:10.1186/bcr3594.PubMedCentralPubMed

117.

Kamei N, Tobe K, Suzuki R, Ohsugi M, Watanabe T, Kubota N, et al. Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J Biol Chem. 2006;281(36):26602–14. doi:10.1074/jbc.M601284200.PubMed

118.

Kanda H, Tateya S, Tamori Y, Kotani K. Hiasa K-i, Kitazawa R et al. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest. 2006;116(6):1494–505.PubMedCentralPubMed

119.

Acedo SC, Gambero S, Cunha FG, Lorand-Metze I, Gambero A. Participation of leptin in the determination of the macrophage phenotype: an additional role in adipocyte and macrophage crosstalk. In Vitro Cell Dev Biol Anim. 2013;49(6):473–8. doi:10.1007/s11626-013-9629-x.PubMed

120.

Klein-Wieringa IR, Andersen SN, Kwekkeboom JC, Giera M, de Lange-Brokaar BJ, van Osch GJ, et al. Adipocytes modulate the phenotype of human macrophages through secreted lipids. J Immunol. 2013;191(3):1356–63. doi:10.4049/jimmunol.1203074.PubMed

121.

Gruen ML, Hao M, Piston DW, Hasty AH. Leptin requires canonical migratory signaling pathways for induction of monocyte and macrophage chemotaxis. Am J Physiol Cell Physiol. 2007;293(5):C1481–8. doi:10.1152/ajpcell.00062.2007.PubMed

122.

Lin Y, Li Q. Expression and function of leptin and its receptor in mouse mammary gland. Sci China C Life Sci. 2007;50(5):669–75. doi:10.1007/s11427-007-0077-2.PubMed

123.

Routley CE, Ashcroft GS. Effect of estrogen and progesterone on macrophage activation during wound healing. Wound Repair Regen. 2009;17(1):42–50. doi:10.1111/j.1524-475X.2008.00440.x.PubMed

124.

Calippe B, Douin-Echinard V, Delpy L, Laffargue M, Lelu K, Krust A, et al. 17Beta-estradiol promotes TLR4-triggered proinflammatory mediator production through direct estrogen receptor alpha signaling in macrophages in vivo. J Immunol. 2010;185(2):1169–76. doi:10.4049/jimmunol.0902383.PubMed

125.

Jensen F, Woudwyk M, Teles A, Woidacki K, Taran F, Costa S, et al. Estradiol and progesterone regulate the migration of mast cells from the periphery to the uterus and induce their maturation and degranulation. PLoS One. 2010;5(12):e14409. doi:10.1371/journal.pone.0014409.PubMedCentralPubMed

126.

Zaitsu M, Narita S, Lambert KC, Grady JJ, Estes DM, Curran EM, et al. Estradiol activates mast cells via a non-genomic estrogen receptor-alpha and calcium influx. Mol Immunol. 2007;44(8):1977–85. doi:10.1016/j.molimm.2006.09.030.PubMedCentralPubMed

127.

Lelu K, Laffont S, Delpy L, Paulet PE, Perinat T, Tschanz SA, et al. Estrogen receptor alpha signaling in T lymphocytes is required for estradiol-mediated inhibition of Th1 and Th17 cell differentiation and protection against experimental autoimmune encephalomyelitis. J Immunol. 2011;187(5):2386–93. doi:10.4049/jimmunol.1101578.PubMed

128.

Pernis AB. Estrogen and CD4+ T cells. Curr Opin Rheumatol. 2007;19(5):414–20. doi:10.1097/BOR.0b013e328277ef2a.PubMed

129.

Tai P, Wang J, Jin H, Song X, Yan J, Kang Y, et al. Induction of regulatory T cells by physiological level estrogen. J Cell Physiol. 2008;214(2):456–64. doi:10.1002/jcp.21221.PubMed

130.

Fu Y, Li L, Liu X, Ma C, Zhang J, Jiao Y, et al. Estrogen promotes B cell activation in vitro through down-regulating CD80 molecule expression. Gynecol Endocrinol. 2011;27(8):593–6. doi:10.3109/09513590.2010.507281.PubMed

131.

Grimaldi CM, Cleary J, Dagtas AS, Moussai D, Diamond B. Estrogen alters thresholds for B cell apoptosis and activation. J Clin Invest. 2002;109(12):1625–33. doi:10.1172/JCI14873.PubMedCentralPubMed

132.

Grimaldi CM, Jeganathan V, Diamond B. Hormonal regulation of B cell development: 17 beta-estradiol impairs negative selection of high-affinity DNA-reactive B cells at more than one developmental checkpoint. J Immunol. 2006;176(5):2703–10.PubMed

133.

Tsutsui S, Yasuda K, Suzuki K, Tahara K, Higashi H, Era S. Macrophage infiltration and its prognostic implications in breast cancer: the relationship with VEGF expression and microvessel density. Oncol Rep. 2005;14(2):425–31.PubMed

134.

Leek RD, Lewis CE, Whitehouse R, Greenall M, Clarke J, Harris AL. Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res. 1996;56(20):4625–9.PubMed

135.

Goede V, Brogelli L, Ziche M, Augustin HG. Induction of inflammatory angiogenesis by monocyte chemoattractant protein-1. Int J Cancer. 1999;82(5):765–70. doi:10.1002/(sici)1097-0215(19990827)82:5<765::aid-ijc23>3.0.co;2-f.PubMed

136.

Lee AH, Happerfield LC, Bobrow LG, Millis RR. Angiogenesis and inflammation in invasive carcinoma of the breast. J Clin Pathol. 1997;50(8):669–73. doi:10.1136/jcp.50.8.669.PubMedCentralPubMed

137.

Volodko N, Reiner A, Rudas M, Jakesz R. Tumour-associated macrophages in breast cancer and their prognostic correlations. Breast. 1998;7(2):99–105. doi:10.1016/S0960-9776(98)90065-0.

138.

McDermott RS, Deneux L, Mosseri V, Vedrenne J, Clough K, Fourquet A, et al. Circulating macrophage colony stimulating factor as a marker of tumour progression. Eur Cytokine Netw. 2002;13(1):121–7.PubMed

139.

Ueno T, Toi M, Saji H, Muta M, Bando H, Kuroi K, et al. Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer. Clin Cancer Res. 2000;6(8):3282–9.PubMed

140.

Lin EY, Nguyen AV, Russell RG, Pollard JW. Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. 2001. p. 727–40.

141.

DeNardo DG, Barreto JB, Andreu P, Vasquez L, Tawfik D, Kolhatkar N, et al. CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell. 2009;16(2):91–102. doi:10.1016/j.ccr.2009.06.018.PubMedCentralPubMed

142.

DeNardo DG, Brennan DJ, Rexhepaj E, Ruffell B, Shiao SL, Madden SF, et al. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discov. 2011;1(1):54–67. doi:10.1158/2159-8274.cd-10-0028.PubMedCentralPubMed

143.

Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ. Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother. 2009;58(1):49–59. doi:10.1007/s00262-008-0523-4.PubMedCentralPubMed

144.

Montero AJ, Diaz-Montero CM, Deutsch YE, Hurley J, Koniaris LG, Rumboldt T, et al. Phase 2 study of neoadjuvant treatment with NOV-002 in combination with doxorubicin and cyclophosphamide followed by docetaxel in patients with HER-2 negative clinical stage II-IIIc breast cancer. Breast Cancer Res Treat. 2012;132(1):215–23. doi:10.1007/s10549-011-1889-0.PubMedCentralPubMed

145.

Ohara M, Yamaguchi Y, Matsuura K, Murakami S, Arihiro K, Okada M. Possible involvement of regulatory T cells in tumor onset and progression in primary breast cancer. Cancer Immunol Immunother. 2009;58(3):441–7.PubMed

146.

Bates GJ, Fox SB, Han C, Leek RD, Garcia JF, Harris AL, et al. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol. 2006;24(34):5373–80.PubMed

147.

Yan M, Jene N, Byrne D, Millar EK, O’Toole SA, McNeil CM, et al. Recruitment of regulatory T cells is correlated with hypoxia-induced CXCR4 expression, and is associated with poor prognosis in basal-like breast cancers. Breast Cancer Res. 2011;13(2):R47. doi:10.1186/bcr2869.PubMedCentralPubMed

148.

Rodriguez PC, Zea AH, Culotta KS, Zabaleta J, Ochoa JB, Ochoa AC. Regulation of T cell receptor CD3zeta chain expression by L-arginine. J Biol Chem. 2002;277(24):21123–9. doi:10.1074/jbc.M110675200.PubMed

149.

Doedens AL, Stockmann C, Rubinstein MP, Liao D, Zhang N, DeNardo DG, et al. Macrophage expression of hypoxia-inducible factor-1 alpha suppresses T-cell function and promotes tumor progression. Cancer Res. 2010;70(19):7465–75. doi:10.1158/0008-5472.CAN-10-1439.PubMedCentralPubMed

150.

Coussens LM, Zitvogel L, Palucka AK. Neutralizing tumor-promoting chronic inflammation: a magic bullet? Science. 2013;339(6117):286–91. doi:10.1126/science.1232227.PubMedCentralPubMed

151.

Fend L, Accart N, Kintz J, Cochin S, Reymann C, Le Pogam F, et al. Therapeutic effects of anti-CD115 monoclonal antibody in mouse cancer models through dual inhibition of tumor-associated macrophages and osteoclasts. PLoS One. 2013;8(9):e73310. doi:10.1371/journal.pone.0073310.PubMedCentralPubMed

152.

Strachan DC, Ruffell B, Oei Y, Bissell MJ, Coussens LM, Pryer N, et al. CSF1R inhibition delays cervical and mammary tumor growth in murine models by attenuating the turnover of tumor-associated macrophages and enhancing infiltration by CD8 T cells. Oncolmmunology. 2013;2(12):e26968. doi:10.4161/onci.26968.

153.

Fridlender ZG, Buchlis G, Kapoor V, Cheng G, Sun J, Singhal S, et al. CCL2 blockade augments cancer immunotherapy. Cancer Res. 2010;70(1):109–18. doi:10.1158/0008-5472.can-09-2326.PubMedCentralPubMed

154.

Eubank TD, Roberts RD, Khan M, Curry JM, Nuovo GJ, Kuppusamy P, et al. Granulocyte macrophage colony-stimulating factor inhibits breast cancer growth and metastasis by invoking an anti-angiogenic program in tumor-educated macrophages. Cancer Res. 2009;69(5):2133–40. doi:10.1158/0008.PubMedCentralPubMed

155.

Zhang X, Tian W, Cai X, Wang X, Dang W, Tang H, et al. Hydrazinocurcumin Encapsuled nanoparticles “re-educate” tumor-associated macrophages and exhibit anti-tumor effects on breast cancer following STAT3 suppression. PLoS One. 2013;8(6):e65896. doi:10.1371/journal.pone.0065896.PubMedCentralPubMed

156.

Faure E, Heisterkamp N, Groffen J, Kaartinen V. Differential expression of TGF-beta isoforms during postlactational mammary gland involution. Cell Tissue Res. 2000;300(1):89–95.PubMed

157.

Nguyen AV, Pollard JW. Transforming growth factor beta3 induces cell death during the first stage of mammary gland involution. Development. 2000;127(14):3107–18.PubMed

158.

Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252–64. doi:10.1038/nrc3239.PubMed

159.

Aliperti LA, Predina JD, Vachani A, Singhal S. Local and systemic recurrence is the Achilles heel of cancer surgery. Ann Surg Oncol. 2011;18(3):603–7. doi:10.1245/s10434-010-1442-0.PubMed

160.

Emens LA. Breast cancer immunobiology driving immunotherapy: vaccines and immune checkpoint blockade. Expert Rev Anticancer Ther. 2012;12(12):1597–611. doi:10.1586/era.12.147.PubMedCentralPubMed

161.

Silanikove N. Natural and abrupt involution of the mammary gland affects differently the metabolic and health consequences of weaning. Life Sci. 2014;102(1):10–5. doi:10.1016/j.lfs.2014.02.034.PubMed

162.

Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature. 2005;438(7069):820–7. doi:10.1038/nature04186.PubMedCentralPubMed

163.

Faupel-Badger JM, Arcaro KF, Balkam JJ, Eliassen AH, Hassiotou F, Lebrilla CB, et al. Postpartum remodeling, lactation, and breast cancer risk: summary of a national cancer institute-sponsored workshop. J Natl Cancer Inst. 2013;105(3):166–74. doi:10.1093/jnci/djs505.PubMedCentralPubMed

164.

Bernier MO, Plu-Bureau G, Bossard N, Ayzac L, Thalabard JC. Breastfeeding and risk of breast cancer: a metaanalysis of published studies. Hum Reprod Update. 2000;6(4):374–86.PubMed

165.

Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50302 women with breast cancer and 96973 women without the disease. Lancet. 2002;360(9328):187–95. doi:10.1016/s0140-6736(02)09454-0.

166.

Michels KB, Willett WC, Rosner BA, Manson JE, Hunter DJ, Colditz GA, et al. Prospective assessment of breastfeeding and breast cancer incidence among 89,887 women. Lancet. 1996;347(8999):431–6.PubMed

167.

Jordan I, Hebestreit A, Swai B, Krawinkel MB. Breast cancer risk among women with long-standing lactation and reproductive parameters at low risk level: a case–control study in Northern Tanzania. Breast Cancer Res Treat. 2013;142(1):133–41. doi:10.1007/s10549-010-1255-7.PubMed

168.

Millikan RC, Newman B, Tse CK, Moorman PG, Conway K, Dressler LG, et al. Epidemiology of basal-like breast cancer. Breast Cancer Res Treat. 2008;109(1):123–39. doi:10.1007/s10549-007-9632-6.PubMedCentralPubMed

169.

Palmer JR, Boggs DA, Wise LA, Ambrosone CB, Adams-Campbell LL, Rosenberg L. Parity and lactation in relation to estrogen receptor negative breast cancer in African American women. Cancer Epidemiol Biomarkers Prev. 2011;20(9):1883–91. doi:10.1158/1055-9965.EPI-11-0465.PubMedCentralPubMed

170.

Li CI, Beaber EF, Tang MT, Porter PL, Daling JR, Malone KE. Reproductive factors and risk of estrogen receptor positive, triple-negative, and HER2-neu overexpressing breast cancer among women 20–44 years of age. Breast Cancer Res Treat. 2013;137(2):579–87. doi:10.1007/s10549-012-2365-1.PubMedCentralPubMed

171.

Stuebe AM, Willett WC, Xue F, Michels KB. Lactation and incidence of premenopausal breast cancer: a longitudinal study. Arch Intern Med. 2009;169(15):1364–71. doi:10.1001/archinternmed.2009.231.PubMedCentralPubMed

172.

Ishida T, Yokoe T, Kasumi F, Sakamoto G, Makita M, Tominaga T, et al. Clinicopathologic characteristics and prognosis of breast cancer patients associated with pregnancy and lactation: analysis of case–control study in Japan. Jpn J Cancer Res. 1992;83(11):1143–9.PubMed

173.

Martinez ME, Wertheim BC, Natarajan L, Schwab R, Bondy M, Daneri-Navarro A, et al. Reproductive factors, heterogeneity, and breast tumor subtypes in women of Mexican descent. Cancer Epidemiol Biomark Prev. 2013;22(10):1853–61. doi:10.1158/1055-9965.epi-13-0560.

174.

Gustbee E, Anesten C, Markkula A, Simonsson M, Rose C, Ingvar C, et al. Excessive milk production during breast-feeding prior to breast cancer diagnosis is associated with increased risk for early events. Springerplus. 2013;2(1):298. doi:10.1186/2193-1801-2-298.PubMedCentralPubMed

175.

Sotgia F, Casimiro MC, Bonuccelli G, Liu M, Whitaker-Menezes D, Er O, et al. Loss of caveolin-3 induces a lactogenic microenvironment that is protective against mammary tumor formation. Am J pathol. 2009;174(2):613–29. doi:10.2353/ajpath.2009.080653.PubMedCentralPubMed

176.

Wyckoff J, Wang W, Lin EY, Wang Y, Pixley F, Stanley ER, et al. A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res. 2004;64(19):7022–9. doi:10.1158/0008-5472.CAN-04-1449.PubMed

Titel: Mammary Gland Involution as an Immunotherapeutic Target for Postpartum Breast Cancer
verfasst von: Jaime Fornetti
Holly A. Martinson
Courtney B. Betts
Traci R. Lyons
Sonali Jindal
Qiuchen Guo
Lisa M. Coussens
Virginia F. Borges
Pepper Schedin
Publikationsdatum: 01.07.2014
Verlag: Springer US
Erschienen in: Journal of Mammary Gland Biology and Neoplasia / Ausgabe 2/2014
Print ISSN: 1083-3021
Elektronische ISSN: 1573-7039
DOI: https://doi.org/10.1007/s10911-014-9322-z

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Umsetzung der POMGAT-Leitlinie läuft

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Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Springer Medizin

Mammary Gland Involution as an Immunotherapeutic Target for Postpartum Breast Cancer

Abstract

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Abstract

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