nach oben

Indian Journal of Surgery

Erschienen in:

01.06.2013 | Review Article

Breast Cancer Stem Cells, Pathways and Therapeutic Perspectives 2011

verfasst von: Anjana Nigam

Erschienen in: Indian Journal of Surgery | Ausgabe 3/2013

Einloggen, um Zugang zu erhalten

Abstract

The evidence for the existence of a heterogeneous population of cancer stem cells (CSCs) responsible for the initiation and maintenance of cancer has been characterized for several tumors recently. Purification and molecular characterization of normal human mammary stem cells from cultured mammospheres has been achieved, providing evidence supporting a model in which breast tumor heterogeneity is a reflection of a number of CSC-like cells in the tumor. A number of experimental methodologies have been developed to characterize epithelial stem cells, including the expression of cell surface or intracellular markers, mammosphere formation, exclusion of fluorescent dye by a side population, retention of the radionucleotide label, etc. Methodologies have also been successfully employed to identify tumorigenic cells within breast cancers. The most important characteristics of stem cells are the capacity for self-renewal and the regulation of the balance between self-renewal and differentiation. In the mammary gland, signaling pathways, such as Hedgehog (Hh), Wnt/β-catenin, and Notch, play a role in embryogenesis and organogenesis and maintenance of tissues in the adult through regulation of the balance between self-renewal and differentiation of stem cells. Breast TAAs include epitopes from proteins, such as carcinoembryonic antigen and NYBR-1, which are involved in tissue differentiation. Targeting BCSCs may be achieved by a number of approaches such as chemotherapy sensitization of BCSCs, differentiating therapy, targeting stem cell elimination, targeting signaling pathways and drug transporters, and inhibition of regulatory pathways involved in self-renewal. Targeting cells which have the potential to metastasize will be an important aspect of the BCSC field as these are the cells that cause the majority of morbidity and mortality from breast cancer.

Kakarala M, Wicha MS (2008) Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy. J Clin Oncol 10(26):2813–2820

Wong JF (2007) Probing the biology of cancer stem cells: AACR sheds light on the microenvironment to better target these cells and their pathways. Genet Eng Biotech News 27(10)

Korkaya H, Paulson A, Iovino F, Wicha MS (2008) HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion. Oncogene 27:6120–6130PubMedCentralPubMed

Chiou SH, Yu CC, Huang CY, Lin SC, Liu CJ, Tsai TH, Chou SH, Chien CS, Ku HH, Lo JF (2008) Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and highgrade oral squamous cell carcinoma. Clin Cancer Res 14:4085–4095PubMed

Okamoto OK, Perez JF (2008) Targeting cancer stem cells with monoclonal antibodies: a new perspective in cancer therapy and diagnosis. Expert Rev MolDiagn 8:387–393

Stiles CD, Rowitch DH (2008) Glioma stem cells: a midterm exam. Neuron 58:832–846PubMed

Annabi B, Rojas-Sutterlin S, Laflamme C, Lachambre MP, Rolland Y, Sartelet H, Beliveau R (2008) Tumor environment dictates medulloblastoma cancer stem cell expression and invasive phenotype. Mol Cancer Res 6:907–916PubMed

Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737PubMed

Singh S, Hawkins C, Clarke I, Squire J, Bayani J, Hide T, Henkelman R, Cusimano M, Dirks P (2004) Identification of human brain tumour initiating cells. Nature 432(7015):396–401PubMed

10.

Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, Pilotti S, Pierotti MA, Daidone MG (2005) Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 65:5506–5511PubMed

11.

Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–3988PubMedCentralPubMed

12.

Pece S, Tosoni D, Confalonieri S, Mazzarol G, Vecchi M, Ronzoni S, Bernard L, Viale G, Pelicci PG, Di Fiore PP (2010) Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell 140(1):62–73PubMed

13.

Soeda A, Park M, Lee D et al (2009) Hypoxia promotes expansion of the CD133− positive glioma stem cells through activation of HIF-1α. Oncogene 28(45):3949–3959PubMed

14.

Chen R, Nishimura MC, Bumbaca SM, Kharbanda S, Forrest WF, Kasman IM, Greve JM, Soriano RH, Gilmour LL, Rivers CS, Modrusan Z, Nacu S, Guerrero S, Edgar KA, Wallin JJ, Lamszus K, Westphal M, Heim S, James CD, Vanden Berg SR, Costello JF, Moorefield S, Cowdrey CJ, Prados M, Phillips HS (2010) A hierarchy of self-renewing tumor-initiating cell types in glioblastoma. Cancer Cell 17:362–375PubMed

15.

Nowell PC (1976) The clonal evolution of tumor cell populations. Science 194:23–28PubMed

16.

Liang Y, Zhong Z, Huang Y, Deng W, Cao J, Tsao G, Liu Q, Pei D, Kang T, Zeng YX (2010) Stem-like cancer cells are inducible by increasing genomic instability in cancer cell. J Biol Chem 285(7):4931–4940PubMedCentralPubMed

17.

Sharma S, Kelly TK, Jones PA (2010) Epigenetics in cancer. Carcinogenesis 31:27–36PubMedCentralPubMed

18.

Li Y, Welm B, Podsypanina K, Huang S, Chamorro M, Zhang X, Rowlands T, Egeblad M, Cowin P, Werb Z et al (2003) Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells. Proc Natl Acad Sci USA 100:15853–15858PubMedCentralPubMed

19.

Lynch MD, Cariati M, Purushotham AD (2006) Breast cancer, stem cells and prospects for therapy. Breast Cancer Res 8:211PubMedCentralPubMed

20.

Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE (2006) Generation of a functional mammary gland from a single stem cell. Nature 439:84–88PubMed

21.

Simic P, Vukicevic S (2005) Bone morphogenetic proteins in development and homeostasis of kidney. Cytokine Growth Factor Rev 16:299–308PubMed

22.

Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2:442–454PubMed

23.

Yingling JM, Blanchard KL, Sawyer JS (2004) Development of TGF-β signalling inhibitors for cancer therapy. Nat Rev Drug Discov 3:1011–1022PubMed

24.

Deckers M, van Dinther M, Buijs J, Que I, Lowik C, van der Pluijm G, ten Dijke P (2006) The tumor suppressor Smad4 is required for transforming growth factor β-induced epithelial to mesenchymal transition and bone metastasis of breast cancer cells. Cancer Res 66:2202–2209PubMed

25.

Buijs JT, Henriquez NV, van Overveld PG, van der Horst G, Que I, Schwaninger R, Rentsch C, Ten Dijke P, Cleton-Jansen AM, Driouch K, Lidereau R, Bachelier R, Vukicevic S, Clézardin P, Papapoulos SE, Cecchini MG, Löwik CW, van der Pluijm G (2007) Bone morphogenetic protein 7 in the development and treatment of bone metastasesfrom breast cancer. Cancer Res 67(18):8742–8751PubMed

26.

Schwalbe M, Sanger J, Eggers R, Naumann A, Schmidt A, Hoffken K, Clement JH (2003) Differential expression and regulation of bone morphogenetic protein 7 in breast cancer. Int J Oncol 23:89–95PubMed

27.

Takahashi M, Otsuka F, Miyoshi T, Otani H, Goto J, Yamashita M, Ogura T, Makino H, Doihara H (2008) Bone morphogenetic protein 6 (BMP6) and BMP7 inhibit estrogen-induced proliferation of breast cancer cells by suppressing p38 mitogen-activated protein kinase activation. J Endocrinol 199(3):445–455PubMed

28.

Wong DJ, Liu H, Ridky TW, Cassarino D, Segal E, Chang HY (2008) Module map of stem cell genes guides creation of epithelial cancer stem cells. Cell Stem Cell 2:333–344PubMedCentralPubMed

29.

Honeth G, Bendahl PO, Ringner M, Saal LH, Gruvberger-Saal SK, Lovgren K, Grabau D, Ferno M, Borg A, Hegardt C (2008) CD44+/CD24-phenotype is enriched in basallike breast tumors. Breast Cancer Res 10:R53PubMedCentralPubMed

30.

Morrison BJ, Schmidt CW, Sunil R, Lakhani SR, Brent A, Reynolds BA, Lopez JA (2008) Breast cancer stem cells: implications for therapy of breast cancer. Breast Cancer Res 10:210PubMedCentralPubMed

31.

Savagner P (2010) The epithelial-mesenchymal transition (EMT) phenomenon. Ann Oncol 21(Suppl 7):vii89–vii92PubMed

32.

Savagner P (2001) Leaving the neighborhood: molecular mechanisms involved during epithelial-mesenchymal transition. Bioessays 23:912–923PubMed

33.

Thiery J (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139:871–890PubMed

34.

Berx G, Raspe E, Christofori G, Thiery JP, Sleeman JP (2007) Pre-EMTing metastasis? Recapitulation of morphogenetic processes in cancer. Clin Exp Metastasis 24:587–597PubMed

35.

Arnoux V, Come C, Kusewitt DF, Hudson L, Savagner P (2005) Cutaneous wound healing: a partial and reversible EMT. In: Savagner P (ed) Rise and Fall of Epithelial Phenotype: Concepts of Epithelial–Mesenchyme Transition. Springer, Berlin, pp 111–134

36.

Morel A, Lievre M, Thomas C, Hinkal G, Ansieau S, Puisieux A (2008) Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS One 3:e2888PubMedCentralPubMed

37.

Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133:704–715PubMedCentralPubMed

38.

Wyatt L, Wadham C, Crocker LA, Lardelli M, Khew-Goodall Y (2007) The protein tyrosine phosphatase Pez regulates TGFbeta, epithelial-mesenchymal transition, and organ development. J Cell Biol 178:1223–1235PubMedCentralPubMed

39.

Waerner T, Alacakaptan M, Tamir I, Oberauer R, Gal A, Brabletz T, Schreiber M, Jechlinger M, Beug H (2006) ILEI: a cytokine essential for EMT, tumor formation, and late events in metastasis in epithelial cells. Cancer Cell 10:227–239PubMed

40.

Beach S, Tang H, Park S, Dhillon AS, Keller ET, Kolch W, Yeung KC (2008) Snail is a repressor of RKIP transcription in metastatic prostate cancer cells. Oncogene 27:2243–2248PubMedCentralPubMed

41.

Zhuang Z, Lininger RA, Man YG, Albuquerque A, Merino MJ, Tavassoli FA (1997) Identical clonality of both components of mammary carcinosarcoma with differential loss of heterozygosity. Mod Pathol 10:354–362PubMed

42.

Saegusa M, Hashimura M, Kuwata T, Okayasu I (2009) Requirement of the Akt/beta-catenin pathway for uterine carcinosarcoma genesis, modulating E-cadherin expression through the transactivation of slug. Am J Pathol 174:2107–2115PubMedCentralPubMed

43.

Berx G, Cleton-Jansen AM, Strumane K, de Leeuw WJ, Nollet F, van Roy F, Cornelisse C (1996) E-cadherin is inactivated in a majority of invasive human lobular breast cancers by truncation mutations throughout its extracellular domain. Oncogene 13:1919–1925PubMed

44.

Moll R, Mitze M, Frixen UH, Birchmeier W (1993) Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas. Am J Pathol 143:1731–1742PubMedCentralPubMed

45.

Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA (2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117:927–939PubMed

46.

Patel SA, Heinrich AC, Reddy BY, Srinivas B, Heidaran N, Rameshwar P (2008) Breast cancer biology: the multifaceted roles of mesenchymal stem cells. J Oncol 2008:425895PubMedCentralPubMed

47.

Greco SJ, Rameshwar P (2007) MicroRNAs regulate synthesis of the neurotransmitter substance P in human mesenchymal stem cell-derived neuronal cells. Proc Natl Acad Sci USA 104(39):15484–15489PubMedCentralPubMed

48.

Metz RL, Patel PS, Hameed M, Bryan M, Rameshwar P (2007) Role of human HGFIN/nmb in breast cancer. Breast Cancer Res 9:1–10

49.

Corcoran KE, Rameshwar P (2007) Nuclear factor-κB accounts for the repressor effects of high stromal cell-derived factor-1α levels on Tac1 expression in nontumorigenic breast cells. Mol Cancer Res 5:373–381PubMed

50.

Pantel K, Brakenhoff RH (2004) Dissecting the metastatic cascade. Nat Rev Cancer 4:448–456PubMed

51.

Cristofanilli M, Hayes D, Budd G, Ellis M, Stopeck A, Reuben J, Doyle G, Matera J, Allard W, Miller M, Fritsche HA, Hortobagyi GN, Terstappen LW (2005) Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 23:1420–1430PubMed

52.

Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verástegui E, Zlotnik A (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410:50–56PubMed

53.

Pang R, Law WL, Chu AC, Poon JT, Lam CS, Chow AK, Ng L, Cheung LW, Lan XR, Lan HY, Tan VP, Yau TC, Poon RT, Wong BC (2010) A subpopulation of CD26+ cancer stem cells with metastatic capacity in human colorectal cancer. Cell Stem Cell 6(6):603–615PubMed

54.

Vaillant F, Asselin-Labat ML, Shackleton M, Lindeman GJ, Visvader JE (2007) The emerging picture of the mouse mammary stem cell. Stem Cell Rev 3:114–123PubMed

55.

Liu S, Ginestier C, Charafe-Jauffret E, Foco H, Kleer CG, Merajver SD, Dontu G, Wicha MS (2008) BRCA1 regulates human mammary stem/progenitor cell fate. Proc Natl Acad Sci USA 105:1680–1685PubMedCentralPubMed

56.

Narod SA, Foulkes WD (2004) BRCA1 and BRCA2: 1994 and beyond. Nat Rev Cancer 4:665–676PubMed

57.

Dontu G, El-Ashry D, Wicha MS (2004) Breast cancer, stem/progenitor cells and the estrogen receptor. Trends Endocrinol Metab 15:193–197PubMed

58.

Gaiano N, Fishell G (2002) The role of Notch in promoting glial and neural stem cell fates. Ann Rev Neurosci 25:471–490PubMed

59.

Uyttendaele H, Soriano JV, Montesano R, Kitajewski J (1998) Notch4 and Wnt-1 proteins function to regulate branching morphogenesis of mammary epithelial cells in an opposing fashion. Dev Biol 196:204–217PubMed

60.

Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ, Wicha MS (2003) In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev 17:1253–1270PubMedCentralPubMed

61.

Tepera SB, McCrea PD, Rosen JM (2003) A beta-catenin survival signal is required for normal lobular development in the mammary gland. J Cell Sci 116:1137–1149PubMed

62.

Schroeder JA, Adriance MC, McConnell EJ, Thompson MC, Pockaj B, Gendler SJ (2002) ErbB-beta-catenin complexes are associated with human infiltrating ductal breast and murine mammary tumor virus (MMTV)-Wnt-1 and MMTV-c-Neu transgenic carcinomas. J Biol Chem 277:22692–22698PubMed

63.

Hahn H, Wicking C, Zaphiropoulos PG, Gailani MR, Shanley S, Chidambaram A, Vorechovsky I, Holmberg E, Unden AB, Gillies S, Negus K, Smyth I, Pressman C, Leffell DJ, Gerrard B, Goldstein AM, Dean M, Toftgard R, Chenevix-Trench G, Wainwright B, Bale AE (1996) Mutations of the human homolog of drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 85:841–851PubMed

64.

Kubo M, Nakamura M, Tasaki A, Yamanaka N, Nakashima H, Nomura M, Kuroki S, Katano M (2004) Hedgehog signaling pathway is a new therapeutic target for patients with breast cancer. Cancer Res 64:6071–6074PubMed

65.

Lewis MT, Ross S, Strickland PA, Sugnet CW, Jimenez E, Scott MP, Daniel CW (1999) Defects in mouse mammary gland development caused by conditional haploinsufficiency of Patched-1. Development 126:5181–5193PubMed

66.

Hui C, Daniel CW (2001) The Gli2 transcription factor is required for normal mouse mammary gland development. Dev Biol 238:133–144PubMed

67.

Theurillat JP, Zurrer-Hardi U, Varga Z, Storz M, Probst-Hensch NM, Seifert B, Fehr MK, Fink D, Ferrone S, Pestalozzi B, Jungbluth AA, Chen YT, Jäger D, Knuth A, Moch H (2007) NY-BR-1 protein expression in breast carcinoma: a mammary gland differentiation antigen as target for cancer immunotherapy. Cancer Immunol Immunother 56:1723–1731PubMed

68.

Pinzon-Charry A, Schmidt C, Lopez JA (2006) Dendritic cell immunotherapy for breast cancer. Expert Opin Biol Ther 6:591–604PubMed

69.

Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Eystein Lønning P, Børresen-Dale AL (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98:10869–10874PubMedCentralPubMed

70.

Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G (2007) ALDH1 Is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1:555–567PubMedCentralPubMed

71.

Miletti-Gonzalez KE, Chen S, Muthukumaran N, Saglimbeni GN, Wu X, Yang J, Apolito K, Shih WJ, Hait WN, Rodriguez-Rodriguez L (2005) The CD44 receptor interacts with P-glycoprotein to promote cell migration and invasion in cancer. Cancer Res 65:6660–6667PubMed

72.

Engelmann K, Shen H, Finn OJ (2008) MCF7 side population cells with characteristics of cancer stem/progenitor cells express the tumor antigen MUC1. Cancer Res 68:2419–2426PubMed

73.

Wright MH, Calcagno AM, Salcido CD, Carlson MD, Ambudkar SV, Varticovski L (2008) Brca1 breast tumors contain distinct CD44+/CD24- and CD133+ cells with cancer stem cell characteristics. Breast Cancer Res 10:R10PubMedCentralPubMed

74.

Phillips T, McBride W, Pajonk F (2006) The response of CD24(-/low)/CD44+ breast cancer initiating cells to radiation. J Natl Cancer Inst 98:1777–1785PubMed

75.

Dean M, Fojo T, Bates S (2005) Tumour stem cells and drug resistance. Nat Rev Cancer 5:275–284PubMed

76.

Norgaard JM, Olesen LH, Hokland P (2004) Changing picture of cellular drug resistance in human leukemia. Crit Rev Oncol Hematol 50:39–49PubMed

77.

Doyle LA, Yang W, Abruzzo LV, Krogmann T, Gao Y, Rishi AK, Ross DD (1998) A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA 95:15665–15670PubMedCentralPubMed

78.

Thomas H, Coley HM (2003) Overcoming multidrug resistance in cancer: an update on the clinical strategy of inhibiting p-glyco-protein. Cancer Control 10:159–165PubMed

79.

Massard C, Deutsch E, Soria JC (2006) Tumour stem cell-targeted treatment: elimination or differentiation. Ann Oncol 17:1620–1624PubMed

80.

Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, Lander ES (2009) Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 138(4):645–659PubMed

81.

Eddy SF, Kane SE, Sonenshein GE (2007) Trastuzumab-resistant HER2-driven breast cancer cells are sensitive to epigallocate-chin-3 gallate. Cancer Res 67:9018–9023PubMed

82.

Ting AH, McGarvey KM, Baylin SB (2006) The cancer epigenome—components andfunctional correlates. Genes Dev 20:3215–3231PubMed

83.

Gunther EJ, Moody SE, Belka GK, Hahn KT, Innocent N, Dugan KD, Cardiff RD, Chodosh LA (2003) Impact of p53 loss on reversal and recurrence of conditional Wnt-induced tumorigenesis. Genes Dev 17:488–501PubMedCentralPubMed

84.

Luu HH, Zhang R, Haydon RC, Rayburn E, Kang Q, Si W, Park JK, Wang H, Peng Y, Jiang W, He TC (2004) Wnt/beta-catenin signaling pathway as a novel cancer drug target. Curr Cancer Drug Targets 4:653–671PubMed

85.

Zhou L, An N, Haydon RC, Zhou Q, Cheng H, Peng Y, Jiang W, Luu HH, Vanichakarn P, Szatkowski JP, Park JY, Breyer B, He TC (2003) Tyrosine kinase inhibitor STI-571/Gleevec down-regulates the beta-catenin signaling activity. Cancer Lett 193:161–170PubMed

86.

Dontu G, Jackson KW, McNicholas E, Kawamura MJ, Abdallah WM, Wicha MS (2004) Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells. Breast Cancer Res 6:R605–R615PubMedCentralPubMed

87.

Li X, Lewis MT, Huang J, Gutierrez C, Osborne CK, Wu MF, Hilsenbeck SG, Pavlick A, Zhang X, Chamness GC, Wong H, Rosen J, Chang JC (2008) Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst 100:672–679PubMed

88.

Ginestier C, Liu S, Diebel ME, Korkaya H, Luo M, Brown M, Wicinski J, Cabaud O, Charafe-Jauffret E, Birnbaum D, Guan JL, Dontu G, Wicha MS (2010) CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J Clin Invest 120(2):485–497PubMedCentralPubMed

89.

Banchereau J, Steinman R (1998) Dendritic cells and the control of immunity. Nature 392:245–252PubMed

90.

Hollenbeak CS, Todd MM, Billingsley EM, Harper G, Dyer AM, Lengerich EJ (2005) Increased incidence of melanoma in renal transplantation recipients. Cancer 104:1962–1967PubMed

91.

Menard S, Tomasic G, Casalini P, Balsari A, Pilotti S, Cascinelli N, Salvadori B, Colnaghi MI, Rilke F (1997) Lymphoid infiltration as a prognostic variable for early-onset breast carcinomas. Clin Cancer Res 3:817–819PubMed

92.

Gabrilovich DI, Corak J, Ciernik IF, Kavanaugh D, Carbone DP (1997) Decreased antigen presentation by dendritic cells in patients with breast cancer. Clin Cancer Res 3:483–490PubMed

93.

Della Bella S, Gennaro M, Vaccari M, Ferraris C, Nicola S, Riva A, Clerici M, Greco M, Villa ML (2003) Altered maturation of peripheral blood dendritic cells in patients with breast cancer. Br J Cancer 89:1463–1472PubMedCentralPubMed

94.

Pinzon-Charry A, Maxwell T, McGuckin MA, Schmidt CW, Furnival C, Lopez JA (2006) Spontaneous apoptosis of blood dendritic cells in patients with breast cancer. Breast Cancer Res 8:R5PubMedCentralPubMed

95.

Mocellin S, Mandruzzato S, Bronte V, Lise M, Nitti D (2004) Part I: Vaccines for solid tumours. Lancet Oncol 5:681–689PubMed

96.

Sakai Y, Morrison BJ, Burke JD, Park JM, Terabe M, Janik JE, Forni G, Berzofsky JA, Morris JC (2004) Vaccination by genetically modified dendritic cells expressing a truncated neu oncogene prevents development of breast cancer in transgenic mice. Cancer Res 64:8022–8028PubMed

97.

Ridgway D (2003) The first 1000 dendritic cell vaccinees. Cancer Invest 21:873–886PubMed

98.

Panelli MC, Wunderlich J, Jeffries J, Wang E, Mixon A, Rosenberg SA, Marincola FM (2000) Phase 1 study in patients with metastatic melanoma of immunization with dendritic cells presenting epitopes derived from the melanoma-associated antigens MART-1 and gp100. J Immunother 23:487–498PubMed

99.

Banchereau J, Palucka AK, Dhodapkar M, Burkeholder S, Taquet N, Rolland A, Taquet S, Coquery S, Wittkowski KM, Bhardwaj N, Pineiro L, Steinman R, Fay J (2001) Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine. Cancer Res 61:6451–6458PubMed

100.

Brossart P, Wirths S, Stuhler G, Reichardt VL, Kanz L, Brugger W (2000) Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptidepulsed dendritic cells. Blood 96:3102–3108PubMed

101.

Wrzesinski C, Paulos CM, Gattinoni L, Palmer DC, Kaiser A, Yu Z, Rosenberg SA, Restifo NP (2007) Hematopoietic stem cells promote the expansion and function of adoptively transferred antitumor CD8+ T cells. J Clin Invest 117:492–501PubMedCentralPubMed

102.

Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA (2002) Stemness: transcriptional profiling of embryonic and adult stem cells. Science 298:597–600PubMed

103.

Li Y, Zhang T, Korkaya H, Liu S, Lee HF, Newman B, Yu Y, Clouthier SG, Schwartz SJ, Wicha MS, Sun D (2010) Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. Clin Cancer Res 16(9):2580–2590PubMedCentralPubMed

104.

Fang F, Balch C, Schilder J, Breen T, Zhang S, Shen C, Li L, Kulesavage C, Snyder AJ, Nephew KP, Matei DE. Cancer, early view (Articles online in advance of print). http://www3.interscience.wiley.com/journal/123500856/abstract

105.

Taborga M, Corcoran KE, Fernandes N, Ramkissoon SH, Rameshwar P (2007) Gcoupled protein receptors and breast cancer progression: potential drug targets. Mini Rev Med Chem 7(3):245–251PubMed

106.

Bandari PS, Qian J, Yehia G, Joshi DD, Maloof PB, Potian J, Oh HS, Gascon P, Harrison JS, Rameshwar P (2003) Hematopoietic growth factor inducible neurokinin-1 type: a transmembrane protein that is similar to neurokinin 1 interacts with substance P. Regul Pept 111(1–3):169–178PubMed

107.

Rameshwar P (2007) Implication of possible therapies targeted for the tachykinergic system with the biology of neurokinin receptors and emerging related proteins. Recent Pat CNS Drug Discov 2(1):79–84PubMed

108.

Kretzschmar M (2000) Transforming growth factor-β and breast cancer: transforming growth factor-β/SMAD signaling defects and cancer. Breast Cancer Res 2:107–115PubMedCentralPubMed

109.

Yang J, Song K, Krebs TL, Jackson MW, Danielpour D (2008) Rb/E2F4 and Smad2/3 link survivin to TGF-β-induced apoptosis and tumor progression. Oncogene 27:5326–5338PubMedCentralPubMed

110.

Oh HS, Moharita A, Potian JG, Whitehead IP, Livingston JC, Castro TA, Patel PS, Rameshwar P (2004) Bone marrow stroma influences transforming growth factor-β production in breast cancer cells to regulate c-myc activation of the preprotachykinin-I gene in breast cancer cells. Cancer Res 64:6327–6336PubMed

111.

Parmiani G, Russo V, Marrari A, Cutolo G, Casati C, Pilla L, Maccalli C, Rivoltini L, Castelli C (2007) Universal and stemness-related tumor antigens: potential use in cancer immunotherapy. Clin Cancer Res 13:5675–5679PubMed

112.

Lou H, Dean M (2007) Targeted therapy for cancer stem cells: the patched pathway and ABC transporters. Oncogene 26:1357–1360PubMed

113.

Hirschmann-Jax C, Foster AE, Wulf GG, Nuchtern JG, Jax TW, Gobel MA (2004) A distinct “side population” of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA 101:14228–14233PubMedCentralPubMed

Titel: Breast Cancer Stem Cells, Pathways and Therapeutic Perspectives 2011
verfasst von: Anjana Nigam
Publikationsdatum: 01.06.2013
Verlag: Springer India
Erschienen in: Indian Journal of Surgery / Ausgabe 3/2013
Print ISSN: 0972-2068
Elektronische ISSN: 0973-9793
DOI: https://doi.org/10.1007/s12262-012-0616-3

Neu im Fachgebiet Chirurgie

Wie erfolgreich ist eine Re-Ablation nach Rezidiv?

23.04.2024 Ablationstherapie Nachrichten

Nach der Katheterablation von Vorhofflimmern kommt es bei etwa einem Drittel der Patienten zu Rezidiven, meist binnen eines Jahres. Wie sich spätere Rückfälle auf die Erfolgschancen einer erneuten Ablation auswirken, haben Schweizer Kardiologen erforscht.

Hinter dieser Appendizitis steckte ein Erreger

23.04.2024 Appendizitis Nachrichten

Schmerzen im Unterbauch, aber sonst nicht viel, was auf eine Appendizitis hindeutete: Ein junger Mann hatte Glück, dass trotzdem eine Laparoskopie mit Appendektomie durchgeführt und der Wurmfortsatz histologisch untersucht wurde.

Mehr Schaden als Nutzen durch präoperatives Aussetzen von GLP-1-Agonisten?

23.04.2024 Operationsvorbereitung Nachrichten

Derzeit wird empfohlen, eine Therapie mit GLP-1-Rezeptoragonisten präoperativ zu unterbrechen. Eine neue Studie nährt jedoch Zweifel an der Notwendigkeit der Maßnahme.

Ureterstriktur: Innovative OP-Technik bewährt sich

19.04.2024 EAU 2024 Kongressbericht

Die Ureterstriktur ist eine relativ seltene Komplikation, trotzdem bedarf sie einer differenzierten Versorgung. In komplexen Fällen wird dies durch die roboterassistierte OP-Technik gewährleistet. Erste Resultate ermutigen.

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Aktuelle BDC Leitlinien-Webinare

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare

CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare

CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske

Dr. med. Benjamin Meyknecht

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare

CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2013

A Rare Case of Penetrating Rectal Injury

Liver Transplantatation- an Overview

RETRACTED ARTICLE: A Comparative Study of Thermal Burns Treated with Topical Heparin and Without Heparin

Retraction Note: Penile Strangulation by Metallic Rings

Isolated tuberculosis of the spleen: A case report and review of literature

Large Animal-Related Injuries in a Rural Population in Northeastern Turkey

Update Chirurgie