nach oben

Erschienen in:

12.06.2019 | Research Paper

Human-specific RNA analysis shows uncoupled epithelial-mesenchymal plasticity in circulating and disseminated tumour cells from human breast cancer xenografts

verfasst von: Anthony Tachtsidis, Anh Viet-Phuong Le, Tony Blick, Devika Gunasinghe, Emma De Sousa, Mark Waltham, Alex Dobrovic, Erik W. Thompson

Erschienen in: Clinical & Experimental Metastasis | Ausgabe 4/2019

Einloggen, um Zugang zu erhalten

Abstract

Blood samples, bone marrow, tumours and metastases where possible were collected from SCID mice bearing orthotopic xenografts of the triple-negative MDA-MB-468 cell line or a transplantable ER-positive patient derived xenograft (ED-03), and assessed using human-specific, tandem-nested RT-qPCR for markers relating to detection of circulating (CTCs) and disseminated tumour cells (DTCs), breast cancer clinicopathology, the ‘cancer stem cell’ phenotype, metabolism, hypoxia and epithelial-mesenchymal plasticity (EMP). Increased levels of SNAI1, ILK, NOTCH1, CK20, and PGR, and a decrease/loss of EPCAM in CTCs/DTCs were observed relative to the primary xenograft across both models. Decreased CD24 and EGFR was restricted to the MDA-MB-468 model, while increased TFF1 was seen in the ED-03 model. The major metabolic regulator PPARGC1A, and several hypoxia-related markers (HIF1A, APLN and BNIP3) were significantly elevated in both models. Increased expression of mesenchymal markers including SNAI1 was seen across both models, however CDH1 did not decrease concordantly, and several other epithelial markers were increased, suggesting an uncoupling of EMP to produce an EMP hybrid or partial-EMT. Single cell analysis of ED-03 CTCs, although limited, indicated uncoupling of the EMP axis in single hybrid cells, rather than distinct pools of epithelial or mesenchymal-enriched cells, however dynamic heterogeneity between CTCs/DTCs cannot be ruled out. Reduced CD24 expression was observed in the MDA-MB-468 CTCs, consistent with the ‘breast cancer stem cell’ phenotype, and metastatic deposits in this model mostly resembled the primary xenografts, consistent with the mesenchymal-epithelial transition paradigm.

Nur mit Berechtigung zugänglich

Weigelt B, Peterse JL, van ‘t Veer LJ (2005) Breast cancer metastasis: markers and models. Nat Rev Cancer 5(8):591–602CrossRefPubMed

Demicheli R, Retsky MW, Hrushesky WJ, Baum M, Gukas ID (2008) The effects of surgery on tumor growth: a century of investigations. Ann Oncol 19(11):1821–1828. https://doi.org/10.1093/annonc/mdn386 CrossRefPubMed

Goss P, Allan AL, Rodenhiser DI, Foster PJ, Chambers AF (2008) New clinical and experimental approaches for studying tumor dormancy: does tumor dormancy offer a therapeutic target? Apmis 116(7–8):552–568. https://doi.org/10.1111/j.1600-0463.2008.001059.x CrossRefPubMed

Schmidt-Kittler O, Ragg T, Daskalakis A, Granzow M, Ahr A, Blankenstein TJ, Kaufmann M, Diebold J, Arnholdt H, Muller P, Bischoff J, Harich D, Schlimok G, Riethmuller G, Eils R, Klein CA (2003) From latent disseminated cells to overt metastasis: genetic analysis of systemic breast cancer progression. Proc Natl Acad Sci USA 100(13):7737–7742. https://doi.org/10.1073/pnas.1331931100 CrossRefPubMedPubMedCentral

Zhang XHF, Wang Q, Gerald W, Hudis CA, Norton L, Smid M, Foekens JA, Massagué J (2009) Latent Bone Metastasis in Breast Cancer Tied to Src-Dependent Survival Signals. Cancer Cell 16(1):67–78. https://doi.org/10.1016/j.ccr.2009.05.017 CrossRefPubMedPubMedCentral

Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC, Schlimok G, Diel IJ, Gerber B, Gebauer G, Pierga JY, Marth C, Oruzio D, Wiedswang G, Solomayer EF, Kundt G, Strobl B, Fehm T, Wong GY, Bliss J, Vincent-Salomon A, Pantel K (2005) A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 353(8):793–802CrossRefPubMed

Miller MC, Doyle GV, Terstappen LW (2010) Significance of circulating tumor cells detected by the cell search system in patients with metastatic breast colorectal and prostate cancer. J Oncol 2010:617421. https://doi.org/10.1155/2010/617421 CrossRefPubMed

Ramirez JM, Fehm T, Orsini M, Cayrefourcq L, Maudelonde T, Pantel K, Alix-Panabieres C (2014) Prognostic relevance of viable circulating tumor cells detected by EPISPOT in metastatic breast cancer patients. Clin Chem 60(1):214–221. https://doi.org/10.1373/clinchem.2013.215079 CrossRefPubMed

Giuliano M, Giordano A, Jackson S, Hess KR, De Giorgi U, Mego M, Handy BC, Ueno NT, Alvarez RH, De Laurentiis M, De Placido S, Valero V, Hortobagyi GN, Reuben JM, Cristofanilli M (2011) Circulating tumor cells as prognostic and predictive markers in metastatic breast cancer patients receiving first-line systemic treatment. Breast Cancer Res 13(3):67CrossRef

10.

Muller V, Riethdorf S, Rack B, Janni W, Fasching PA, Solomayer E, Aktas B, Kasimir-Bauer S, Pantel K, Fehm T (2012) Prognostic impact of circulating tumor cells assessed with the cell search system and AdnaTest breast in metastatic breast cancer patients: the DETECT study. Breast Cancer Res 14(4):R118. https://doi.org/10.1186/bcr3243 CrossRefPubMedPubMedCentral

11.

Peeters DJ, van Dam PJ, Van den Eynden GG, Rutten A, Wuyts H, Pouillon L, Peeters M, Pauwels P, Van Laere SJ, van Dam PA, Vermeulen PB, Dirix LY (2014) Detection and prognostic significance of circulating tumour cells in patients with metastatic breast cancer according to immunohistochemical subtypes. Br J Cancer 110(2):375–383. https://doi.org/10.1038/bjc.2013.743 CrossRefPubMed

12.

Rack B, Schindlbeck C, Juckstock J, Andergassen U, Hepp P, Zwingers T, Friedl TW, Lorenz R, Tesch H, Fasching PA, Fehm T, Schneeweiss A, Lichtenegger W, Beckmann MW, Friese K, Pantel K, Janni W, on behalf of the SSG (2014) Circulating tumor cells predict survival in early average-to-high risk breast cancer patients. J Natl Cancer Inst. https://doi.org/10.1093/jnci/dju066 CrossRefPubMedPubMedCentral

13.

Zhang L, Riethdorf S, Wu G, Wang T, Yang K, Peng G, Liu J, Pantel K (2012) Meta-analysis of the prognostic value of circulating tumor cells in breast cancer. Clin Cancer Res 18(20):5701–5710. https://doi.org/10.1158/1078-0432.CCR-12-1587 CrossRefPubMed

14.

Janni W, Vogl FD, Wiedswang G, Synnestvedt M, Fehm T, Juckstock J, Borgen E, Rack B, Braun S, Sommer H, Solomayer E, Pantel K, Nesland J, Friese K, Naume B (2011) Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse–a European pooled analysis. Clin Cancer Res 17(9):2967–2976. https://doi.org/10.1158/1078-0432.ccr-10-2515 CrossRefPubMed

15.

Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, Somerfield MR, Hayes DF, Bast RC Jr, American Society of Clinical O (2007) American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol 25(33):5287–5312. https://doi.org/10.1200/jco.2007.14.2364 CrossRefPubMed

16.

Smerage JB, Barlow WE, Hortobagyi GN, Winer EP, Leyland-Jones B, Srkalovic G, Tejwani S, Schott AF, O’Rourke MA, Lew DL, Doyle GV, Gralow JR, Livingston RB, Hayes DF (2014) Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J Clin Oncol 32(31):3483–3489. https://doi.org/10.1200/jco.2014.56.2561 CrossRefPubMedPubMedCentral

17.

Helissey C, Berger F, Cottu P, Dieras V, Mignot L, Servois V, Bouleuc C, Asselain B, Pelissier S, Vaucher I, Pierga JY, Bidard FC (2015) Circulating tumor cell thresholds and survival scores in advanced metastatic breast cancer: the observational step of the CirCe01 phase III trial. Cancer Lett 360(2):213–218. https://doi.org/10.1016/j.canlet.2015.02.010 CrossRefPubMed

18.

Alix-Panabieres C, Mader S, Pantel K (2017) Epithelial-mesenchymal plasticity in circulating tumor cells. J Mol Med 95(2):133–142. https://doi.org/10.1007/s00109-016-1500-6 CrossRefPubMed

19.

Francart ME, Lambert J, Vanwynsberghe AM, Thompson EW, Bourcy M, Polette M, Gilles C (2017) Epithelial-mesenchymal plasticity and circulating tumor cells: travel companions to metastases. Dev Dyn. https://doi.org/10.1002/dvdy.24506 CrossRefPubMed

20.

Polyak K, Weinberg RA (2009) Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 9(4):265–273CrossRefPubMed

21.

van der Pluijm G (2011) Epithelial plasticity, cancer stem cells and bone metastasis formation. Bone 48(1):37–43CrossRefPubMed

22.

Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Ting DT, Isakoff SJ, Ciciliano JC, Wells MN, Shah AM, Concannon KF, Donaldson MC, Sequist LV, Brachtel E, Sgroi D, Baselga J, Ramaswamy S, Toner M, Haber DA, Maheswaran S (2013) Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science 339(6119):580–584. https://doi.org/10.1126/science.1228522 CrossRefPubMedPubMedCentral

23.

Bonnomet A, Syne L, Brysse A, Feyereisen E, Thompson EW, Noel A, Foidart JM, Birembaut P, Polette M, Gilles C (2011) A dynamic in vivo model of epithelial-to-mesenchymal transitions in circulating tumor cells and metastases of breast cancer. Oncogene. https://doi.org/10.1038/onc.2011.540 CrossRefPubMed

24.

Giordano A, Gao H, Anfossi S, Cohen E, Mego M, Lee BN, Tin S, De Laurentiis M, Parker CA, Alvarez RH, Valero V, Ueno NT, De Placido S, Mani SA, Esteva FJ, Cristofanilli M, Reuben JM (2012) Epithelial-mesenchymal transition and stem cell markers in patients with HER2-positive metastatic breast cancer. Mol Cancer Ther 11(11):2526–2534. https://doi.org/10.1158/1535-7163.mct-12-0460 CrossRefPubMedPubMedCentral

25.

Zhang L, Ridgway LD, Wetzel MD, Ngo J, Yin W, Kumar D, Goodman JC, Groves MD, Marchetti D (2013) The identification and characterization of breast cancer CTCs competent for brain metastasis. Sci Transl Med 5(180):180ra148. https://doi.org/10.1126/scitranslmed.3005109 CrossRef

26.

Vishnoi M, Peddibhotla S, Yin W, Scamardo AT, George GC, Hong DS, Marchetti D (2015) The isolation and characterization of CTC subsets related to breast cancer dormancy. Sci Rep 5:17533. https://doi.org/10.1038/srep17533 CrossRefPubMedPubMedCentral

27.

Khoo BL, Lee SC, Kumar P, Tan TZ, Warkiani ME, Ow SG, Nandi S, Lim CT, Thiery JP (2015) Short-term expansion of breast circulating cancer cells predicts response to anti-cancer therapy. Oncotarget 6(17):15578–15593CrossRefPubMedPubMedCentral

28.

Gunasinghe NP, Wells A, Thompson EW, Hugo HJ (2012) Mesenchymal-epithelial transition (MET) as a mechanism for metastatic colonisation in breast cancer. Cancer Metastasis Rev 31(3–4):469–478. https://doi.org/10.1007/s10555-012-9377-5 CrossRefPubMed

29.

Gyorffy B, Lanczky A, Eklund AC, Denkert C, Budczies J, Li Q, Szallasi Z (2010) An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1809 patients. Breast Cancer Res Treat 123(3):725–731. https://doi.org/10.1007/s10549-009-0674-9 CrossRefPubMed

30.

Simmons MJ, Serra R, Hermance N, Kelliher MA (2012) NOTCH1 inhibition in vivo results in mammary tumor regression and reduced mammary tumorsphere forming activity in vitro. Breast Cancer Res 14(5):R126. https://doi.org/10.1186/bcr3321 CrossRefPubMedPubMedCentral

31.

Peng X, Li F, Wang P, Jia S, Sun L, Huo H (2015) Apelin-13 induces MCF-7 cell proliferation and invasion via phosphorylation of ERK1/2. Int J Mol Med 36(3):733–738. https://doi.org/10.3892/ijmm.2015.2265 CrossRefPubMed

32.

Zeisberg M, Shah AA, Kalluri R (2005) Bone morphogenic protein-7 induces mesenchymal to epithelial transition in adult renal fibroblasts and facilitates regeneration of injured kidney. J Biol Chem 280(9):8094–8100. https://doi.org/10.1074/jbc.M413102200 CrossRefPubMed

33.

Alarmo EL, Korhonen T, Kuukasjarvi T, Huhtala H, Holli K, Kallioniemi A (2008) Bone morphogenetic protein 7 expression associates with bone metastasis in breast carcinomas. Ann Oncol 19(2):308–314. https://doi.org/10.1093/annonc/mdm453 CrossRefPubMed

34.

Alarmo EL, Parssinen J, Ketolainen JM, Savinainen K, Karhu R, Kallioniemi A (2009) BMP7 influences proliferation, migration, and invasion of breast cancer cells. Cancer Lett 275(1):35–43. https://doi.org/10.1016/j.canlet.2008.09.028 CrossRefPubMed

35.

Xu J, Zhang W, Tang L, Chen W, Guan X (2018) Epithelial-mesenchymal transition induced PAI-1 is associated with prognosis of triple-negative breast cancer patients. Gene 670:7–14. https://doi.org/10.1016/j.gene.2018.05.089 CrossRefPubMed

36.

Azimi I, Petersen RM, Thompson EW, Roberts-Thomson SJ, Monteith GR (2017) Hypoxia-induced reactive oxygen species mediate N-cadherin and SERPINE1 expression, EGFR signalling and motility in MDA-MB-468 breast cancer cells. Sci Rep 7(1):15140. https://doi.org/10.1038/s41598-017-15474-7 CrossRefPubMedPubMedCentral

37.

Onstenk W, Sieuwerts AM, Weekhout M, Mostert B, Reijm EA, van Deurzen CH, Bolt-de Vries JB, Peeters DJ, Hamberg P, Seynaeve C, Jager A, de Jongh FE, Smid M, Dirix LY, Kehrer DF, van Galen A, Ramirez-Moreno R, Kraan J, Van M, Gratama JW, Martens JW, Foekens JA, Sleijfer S (2015) Gene expression profiles of circulating tumor cells versus primary tumors in metastatic breast cancer. Cancer Lett 362(1):36–44. https://doi.org/10.1016/j.canlet.2015.03.020 CrossRefPubMed

38.

LeBleu VS, O’Connell JT, Gonzalez Herrera KN, Wikman H, Pantel K, Haigis MC, de Carvalho FM, Damascena A, Domingos Chinen LT, Rocha RM, Asara JM, Kalluri R (2014) PGC-1alpha mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis. Nat Cell Biol 16(10):992–1003. https://doi.org/10.1038/ncb3039 1001–1015 CrossRefPubMedPubMedCentral

39.

Helzer KT, Barnes HE, Day L, Harvey J, Billings PR, Forsyth A (2009) Circulating tumor cells are transcriptionally similar to the primary tumor in a murine prostate model. Cancer Res 69(19):7860–7866. https://doi.org/10.1158/0008-5472.can-09-0801 CrossRefPubMed

40.

Sieuwerts AM, Kraan J, Bolt-de Vries J, van der Spoel P, Mostert B, Martens JW, Gratama JW, Sleijfer S, Foekens JA (2009) Molecular characterization of circulating tumor cells in large quantities of contaminating leukocytes by a multiplex real-time PCR. Breast Cancer Res Treat 118(3):455–468. https://doi.org/10.1007/s10549-008-0290-0 CrossRefPubMed

41.

Powell AA, Talasaz AH, Zhang H, Coram MA, Reddy A, Deng G, Telli ML, Advani RH, Carlson RW, Mollick JA, Sheth S, Kurian AW, Ford JM, Stockdale FE, Quake SR, Pease RF, Mindrinos MN, Bhanot G, Dairkee SH, Davis RW, Jeffrey SS (2012) Single cell profiling of circulating tumor cells: transcriptional heterogeneity and diversity from breast cancer cell lines. PLoS ONE 7(5):e33788CrossRefPubMedPubMedCentral

42.

Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA, Yu M, Pely A, Engstrom A, Zhu H, Brannigan BW, Kapur R, Stott SL, Shioda T, Ramaswamy S, Ting DT, Lin CP, Toner M, Haber DA, Maheswaran S (2014) Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell 158(5):1110–1122. https://doi.org/10.1016/j.cell.2014.07.013 CrossRefPubMedPubMedCentral

43.

Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2(8):563–572CrossRefPubMed

44.

Jacob K, Sollier C, Jabado N (2007) Circulating tumor cells: detection, molecular profiling and future prospects. Expert Rev Proteom 4(6):741–756CrossRef

45.

Croker AK, Allan AL (2008) Cancer stem cells: implications for the progression and treatment of metastatic disease. J Cell Mol Med 12(2):374–390. https://doi.org/10.1111/j.1582-4934.2007.00211.x CrossRefPubMed

46.

Luzzi KJ, MacDonald IC, Schmidt EE, Kerkvliet N, Morris VL, Chambers AF, Groom AC (1998) Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. Am J Pathol 153(3):865–873CrossRefPubMedPubMedCentral

47.

Merino D, Weber TS, Serrano A, Vaillant F, Liu K, Pal B, Di Stefano L, Schreuder J, Lin D, Chen Y, Asselin-Labat ML, Schumacher TN, Cameron D, Smyth GK, Papenfuss AT, Lindeman GJ, Visvader JE, Naik SH (2019) Barcoding reveals complex clonal behavior in patient-derived xenografts of metastatic triple negative breast cancer. Nat Commun 10(1):766. https://doi.org/10.1038/s41467-019-08595-2 CrossRefPubMedPubMedCentral

48.

Balic M, Lin H, Young L, Hawes D, Giuliano A, McNamara G, Datar RH, Cote RJ (2006) Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin Cancer Res 12(19):5615–5621CrossRefPubMed

49.

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(7):3983–3988. https://doi.org/10.1073/pnas.0530291100 CrossRefPubMedPubMedCentral

50.

Gorges TM, Tinhofer I, Drosch M, Roese L, Zollner TM, Krahn T, von Ahsen O (2012) Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition. BMC Cancer 12(1):178CrossRefPubMedPubMedCentral

51.

Mego M, Mani SA, Lee BN, Li C, Evans KW, Cohen EN, Gao H, Jackson SA, Giordano A, Hortobagyi GN, Cristofanilli M, Lucci A, Reuben JM (2011) Expression of epithelial-mesenchymal transition-inducing transcription factors in primary breast cancer: the effect of neoadjuvant therapy. Int J Cancer. https://doi.org/10.1002/ijc.26037 CrossRefPubMedPubMedCentral

52.

Wang J, Fu L, Gu F, Ma Y (2011) Notch1 is involved in migration and invasion of human breast cancer cells. Oncol Rep 26(5):1295–1303. https://doi.org/10.3892/or.2011.1399 CrossRefPubMed

53.

Providence KM, Higgins PJ (2004) PAI-1 expression is required for epithelial cell migration in two distinct phases of in vitro wound repair. J Cell Physiol 200(2):297–308. https://doi.org/10.1002/jcp.20016 CrossRefPubMed

54.

Providence KM, Kutz SM, Staiano-Coico L, Higgins PJ (2000) PAI-1 gene expression is regionally induced in wounded epithelial cell monolayers and required for injury repair. J Cell Physiol 182(2):269–280CrossRefPubMed

55.

Chu W, Song X, Yang X, Ma L, Zhu J, He M, Wang Z, Wu Y (2014) Neuropilin-1 promotes epithelial-to-mesenchymal transition by stimulating nuclear factor-kappa B and is associated with poor prognosis in human oral squamous cell carcinoma. PLoS ONE 9(7):e101931. https://doi.org/10.1371/journal.pone.0101931 CrossRefPubMedPubMedCentral

56.

Tse BWC, Volpert M, Ratther E, Stylianou N, Nouri M, McGowan K, Lehman ML, McPherson SJ, Roshan-Moniri M, Butler MS, Caradec J, Gregory-Evans CY, McGovern J, Das R, Takhar M, Erho N, Alshalafa M, Davicioni E, Schaeffer EM, Jenkins RB, Ross AE, Karnes RJ, Den RB, Fazli L, Gregory PA, Gleave ME, Williams ED, Rennie PS, Buttyan R, Gunter JH, Selth LA, Russell PJ, Nelson CC, Hollier BG (2017) Neuropilin-1 is upregulated in the adaptive response of prostate tumors to androgen-targeted therapies and is prognostic of metastatic progression and patient mortality. Oncogene 36(24):3417–3427. https://doi.org/10.1038/onc.2016.482 CrossRefPubMedPubMedCentral

57.

Liu S, Cong Y, Wang D, Sun Y, Deng L, Liu Y, Martin-Trevino R, Shang L, McDermott SP, Landis MD, Hong S, Adams A, D’Angelo R, Ginestier C, Charafe-Jauffret E, Clouthier SG, Birnbaum D, Wong ST, Zhan M, Chang JC, Wicha MS (2014) Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts. Stem Cell Rep 2(1):78–91CrossRef

58.

Bierie B, Pierce SE, Kroeger C, Stover DG, Pattabiraman DR, Thiru P, Liu Donaher J, Reinhardt F, Chaffer CL, Keckesova Z, Weinberg RA (2017) Integrin-beta4 identifies cancer stem cell-enriched populations of partially mesenchymal carcinoma cells. Proc Natl Acad Sci USA 114(12):E2337–e2346. https://doi.org/10.1073/pnas.1618298114 CrossRefPubMedPubMedCentral

59.

Bourcy M, Suarez-Carmona M, Lambert J, Francart ME, Schroeder H, Delierneux C, Skrypek N, Thompson EW, Jerusalem G, Berx G, Thiry M, Blacher S, Hollier BG, Noel A, Oury C, Polette M, Gilles C (2016) Tissue factor induced by epithelial-mesenchymal transition triggers a procoagulant state that drives metastasis of circulating tumor cells. Cancer Res 76(14):4270–4282. https://doi.org/10.1158/0008-5472.can-15-2263 CrossRefPubMed

60.

Cayrefourcq L, Mazard T, Joosse S, Solassol J, Ramos J, Assenat E, Schumacher U, Costes V, Maudelonde T, Pantel K, Alix-Panabieres C (2015) Establishment and characterization of a cell line from human circulating colon cancer cells. Cancer Res 75(5):892–901. https://doi.org/10.1158/0008-5472.can-14-2613 CrossRefPubMed

61.

Lo HW, Hsu SC, Xia W, Cao X, Shih JY, Wei Y, Abbruzzese JL, Hortobagyi GN, Hung MC (2007) Epidermal growth factor receptor cooperates with signal transducer and activator of transcription 3 to induce epithelial-mesenchymal transition in cancer cells via up-regulation of TWIST gene expression. Cancer Res 67(19):9066–9076. https://doi.org/10.1158/0008-5472.can-07-0575 CrossRefPubMedPubMedCentral

62.

Cursons J, Leuchowius KJ, Waltham M, Tomaskovic-Crook E, Foroutan M, Bracken CP, Redfern A, Crampin EJ, Street I, Davis MJ, Thompson EW (2015) Stimulus-dependent differences in signalling regulate epithelial-mesenchymal plasticity and change the effects of drugs in breast cancer cell lines. Cell Commun Signal 13:26. https://doi.org/10.1186/s12964-015-0106-x CrossRefPubMedPubMedCentral

63.

Jahidin AH, Stewart TA, Thompson EW, Roberts-Thomson SJ, Monteith GR (2016) Differential effects of two-pore channel protein 1 and 2 silencing in MDA-MB-468 breast cancer cells. Biochem Biophys Res Commun 477(4):731–736. https://doi.org/10.1016/j.bbrc.2016.06.127 CrossRefPubMed

64.

Stewart TA, Azimi I, Brooks AJ, Thompson EW, Roberts-Thomson SJ, Monteith GR (2016) Janus kinases and Src family kinases in the regulation of EGF-induced vimentin expression in MDA-MB-468 breast cancer cells. Int J Biochem Cell Biol 76:64–74. https://doi.org/10.1016/j.biocel.2016.05.007 CrossRefPubMed

65.

Hugo HJ, Gunasinghe N, Hollier BG, Tanaka T, Blick T, Toh A, Hill P, Gilles C, Waltham M, Thompson EW (2017) Epithelial requirement for in vitro proliferation and xenograft growth and metastasis of MDA-MB-468 human breast cancer cells: oncogenic rather than tumor-suppressive role of E-cadherin. Breast Cancer Res 19(1):86. https://doi.org/10.1186/s13058-017-0880-z CrossRefPubMedPubMedCentral

66.

McCart Reed AE, Kutasovic JR, Vargas AC, Jayanthan J, Al-Murrani A, Reid LE, Chambers R, Da Silva L, Melville L, Evans E, Porter A, Papadimos D, Thompson EW, Lakhani SR, Simpson PT (2016) An epithelial to mesenchymal transition programme does not usually drive the phenotype of invasive lobular carcinomas. J Pathol 238(4):489–494. https://doi.org/10.1002/path.4668 CrossRefPubMed

67.

Kallergi G, Markomanolaki H, Giannoukaraki V, Papadaki MA, Strati A, Lianidou ES, Georgoulias V, Mavroudis D, Agelaki S (2009) Hypoxia-inducible factor-1alpha and vascular endothelial growth factor expression in circulating tumor cells of breast cancer patients. Breast Cancer Res 11(6):R84. https://doi.org/10.1186/bcr2452 CrossRefPubMedPubMedCentral

68.

Ameri K, Luong R, Zhang H, Powell AA, Montgomery KD, Espinosa I, Bouley DM, Harris AL, Jeffrey SS (2010) Circulating tumour cells demonstrate an altered response to hypoxia and an aggressive phenotype. Br J Cancer 102:561CrossRefPubMedPubMedCentral

69.

Li H, Batth IS, Qu X, Xu L, Song N, Wang R, Liu Y (2017) IGF-IR signaling in epithelial to mesenchymal transition and targeting IGF-IR therapy: overview and new insights. Mol Cancer 16(1):6. https://doi.org/10.1186/s12943-016-0576-5 CrossRefPubMedPubMedCentral

70.

Vazquez-Martin A, Cufi S, Oliveras-Ferraros C, Torres-Garcia VZ, Corominas-Faja B, Cuyas E, Bonavia R, Visa J, Martin-Castillo B, Barrajon-Catalan E, Micol V, Bosch-Barrera J, Menendez JA (2013) IGF-1R/epithelial-to-mesenchymal transition (EMT) crosstalk suppresses the erlotinib-sensitizing effect of EGFR exon 19 deletion mutations. Sci Rep 3:2560. https://doi.org/10.1038/srep02560 CrossRefPubMedPubMedCentral

71.

Chaffer CL, San Juan BP, Lim E, Weinberg RA (2016) EMT, cell plasticity and metastasis. Cancer Metastasis Rev 35(4):645–654. https://doi.org/10.1007/s10555-016-9648-7 CrossRefPubMed

72.

Thompson EW, Haviv I (2011) The social aspects of EMT-MET plasticity. Nat Med 17(9):1048–1049CrossRefPubMed

73.

van Denderen BJ, Thompson EW (2013) Cancer: the to and fro of tumour spread. Nature 493(7433):487–488. https://doi.org/10.1038/493487a CrossRefPubMed

74.

Brabletz T, Kalluri R, Nieto MA, Weinberg RA (2018) EMT in cancer. Nat Rev Cancer 18(2):128–134. https://doi.org/10.1038/nrc.2017.118 CrossRefPubMed

75.

Fischer KR, Durrans A, Lee S, Sheng J, Li F, Wong ST, Choi H, El Rayes T, Ryu S, Troeger J, Schwabe RF, Vahdat LT, Altorki NK, Mittal V, Gao D (2015) Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature 527(7579):472–476. https://doi.org/10.1038/nature15748 CrossRefPubMedPubMedCentral

76.

Ye X, Brabletz T, Kang Y, Longmore GD, Nieto MA, Stanger BZ, Yang J, Weinberg RA (2017) Upholding a role for EMT in breast cancer metastasis. Nature 547(7661):E1–e3. https://doi.org/10.1038/nature22816 CrossRefPubMedPubMedCentral

77.

Pastushenko I, Brisebarre A, Sifrim A, Fioramonti M, Revenco T, Boumahdi S, Van Keymeulen A, Brown D, Moers V, Lemaire S, De Clercq S, Minguijon E, Balsat C, Sokolow Y, Dubois C, De Cock F, Scozzaro S, Sopena F, Lanas A, D’Haene N, Salmon I, Marine JC, Voet T, Sotiropoulou PA, Blanpain C (2018) Identification of the tumour transition states occurring during EMT. Nature 556(7702):463–468. https://doi.org/10.1038/s41586-018-0040-3 CrossRefPubMed

78.

Chantrill LA, Nagrial AM, Watson C, Johns AL, Martyn-Smith M, Simpson S, Mead S, Jones MD, Samra JS, Gill AJ, Watson N, Chin VT, Humphris JL, Chou A, Brown B, Morey A, Pajic M, Grimmond SM, Chang DK, Thomas D, Sebastian L, Sjoquist K, Yip S, Pavlakis N, Asghari R, Harvey S, Grimison P, Simes J, Biankin AV (2015) Precision medicine for advanced pancreas cancer: the Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial. Clin Cancer Res 21(9):2029–2037. https://doi.org/10.1158/1078-0432.ccr-15-0426 CrossRefPubMed

79.

Ferrer I, Zugazagoitia J, Herbertz S, John W, Paz-Ares L, Schmid-Bindert G (2018) KRAS-mutant non-small cell lung cancer: from biology to therapy. Lung Cancer 124:53–64. https://doi.org/10.1016/j.lungcan.2018.07.013 CrossRefPubMed

80.

Lafleur MA, Drew AF, de Sousa EL, Blick T, Bills M, Walker EC, Williams ED, Waltham M, Thompson EW (2005) Upregulation of matrix metalloproteinases (MMPs) in breast cancer xenografts: a major induction of stromal MMP-13. Int J Cancer 114(4):544–554. https://doi.org/10.1002/ijc.20763 CrossRefPubMed

Titel: Human-specific RNA analysis shows uncoupled epithelial-mesenchymal plasticity in circulating and disseminated tumour cells from human breast cancer xenografts
verfasst von: Anthony Tachtsidis
Anh Viet-Phuong Le
Tony Blick
Devika Gunasinghe
Emma De Sousa
Mark Waltham
Alex Dobrovic
Erik W. Thompson
Publikationsdatum: 12.06.2019
Verlag: Springer Netherlands
Erschienen in: Clinical & Experimental Metastasis / Ausgabe 4/2019
Print ISSN: 0262-0898
Elektronische ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-019-09977-y

Springer Medizin

Human-specific RNA analysis shows uncoupled epithelial-mesenchymal plasticity in circulating and disseminated tumour cells from human breast cancer xenografts

Abstract

Neu im Fachgebiet Onkologie

Labor, CT-Anthropometrie zeigen Risiko für Pankreaskrebs

Viel pflanzliche Nahrung, seltener Prostata-Ca.-Progression

Alter verschlechtert Prognose bei Endometriumkarzinom

Darf man die Behandlung eines Neonazis ablehnen?

Update Onkologie

Springer Medizin

Abstract

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

Weitere Artikel der Ausgabe 4/2019

Stereotactic radiation therapy in oligometastatic colorectal cancer: outcome of 102 patients and 150 lesions

Diagnostics of metastasis: an increasing challenge with high clinical importance

Metastasis is impaired by endothelial-specific Dll4 loss-of-function through inhibition of epithelial-to-mesenchymal transition and reduction of cancer stem cells and circulating tumor cells

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for endometrial cancer-derived peritoneal metastases: a systematic review

The clinical outcome of eribulin treatment in Japanese patients with advanced soft tissue sarcoma: a Tokai Musculoskeletal Oncology Consortium study

Histopathological growth patterns of colorectal liver metastasis exhibit little heterogeneity and can be determined with a high diagnostic accuracy

Neu im Fachgebiet Onkologie

Labor, CT-Anthropometrie zeigen Risiko für Pankreaskrebs

Viel pflanzliche Nahrung, seltener Prostata-Ca.-Progression

Alter verschlechtert Prognose bei Endometriumkarzinom

Darf man die Behandlung eines Neonazis ablehnen?

Update Onkologie