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01-01-2012 | Research Paper

Hepatocyte induced re-expression of E-cadherin in breast and prostate cancer cells increases chemoresistance

Authors: Yvonne Chao, Qian Wu, Christopher Shepard, Alan Wells

Published in: Clinical & Experimental Metastasis | Issue 1/2012

Abstract

Post-extravasation survival is a key rate-limiting step of metastasis; however, not much is known about the factors that enable survival of the metastatic cancer cell at the secondary site. Furthermore, metastatic nodules are often refractory to current therapies, necessitating the elucidation of molecular changes that affect the chemosensitivity of metastases. Drug resistance exhibited by tumor spheroids has been shown to be mediated by cell adhesion and can be abrogated by addition of E-cadherin blocking antibody. We have previously shown that hepatocyte coculture induces the re-expression of E-cadherin in breast and prostate cancer cells. In this study, we show that this E-cadherin re-expression confers a survival advantage, particularly in the liver microenvironment. E-cadherin re-expression in MDA-MB-231 breast cancer cells resulted in increased attachment to hepatocytes. This heterotypic adhesion between cancer cells and secondary organ parenchymal cells activated ERK MAP kinase, suggesting a functional pro-survival role for E-cadherin during metastatic colonization of the liver. In addition, breast cancer cells that re-expressed E-cadherin in hepatocyte coculture were more chemoresistant compared to 231-shEcad cells unable to re-express E-cadherin. Similar results were obtained in DU-145 prostate cancer cells induced to re-express E-cadherin in hepatocyte coculture or following chemical induction by the GnRH agonist buserelin or the EGFR inhibitor PD153035. These results suggest that E-cadherin re-expression and other molecular changes imparted by a partial mesenchymal to epithelial reverting transition at the secondary site increase post-extravasation survival of the metastatic cancer cell and may help to elucidate why chemotherapy commonly fails to treat metastatic breast cancer.

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Viadana E, Bross ID, Pickren JW (1973) An autopsy study of some routes of dissemination of cancer of the breast. Br J Cancer 27(4):336–340PubMedCrossRef

Lermite E, Marzano E, Chereau E et al (2010) Surgical resection of liver metastases from breast cancer. Surg Oncol 19(4):e79–e84PubMedCrossRef

Atalay G, Biganzoli L, Renard F et al (2003) Clinical outcome of breast cancer patients with liver metastases alone in the anthracycline-taxane era: a retrospective analysis of two prospective, randomised metastatic breast cancer trials. Eur J Cancer 39(17):2439–2449PubMedCrossRef

Diamond JR, Finlayson CA, Borges VF (2009) Hepatic complications of breast cancer. Lancet Oncol 10(6):615–621PubMedCrossRef

Wells A, Chao Y, Wu Q (2011) Biology of metastatic liver tumors. In: Monga SPS (ed) Molecular pathology of liver diseases. Springer, New York, pp 859–866CrossRef

Viadana E, Cotter R, Pickren JW et al (1973) An autopsy study of metastatic sites of breast cancer. Cancer Res 33(1):179–181PubMed

Gassmann P, Hemping-Bovenkerk A, Mees ST et al (2009) Metastatic tumor cell arrest in the liver-lumen occlusion and specific adhesion are not exclusive. Int J Colorectal Dis 24(7):851–858PubMedCrossRef

Glinskii OV, Huxley VH, Glinsky GV et al (2005) Mechanical entrapment is insufficient and intercellular adhesion is essential for metastatic cell arrest in distant organs. Neoplasia 7(5):522–527PubMedCrossRef

McGuire EJ, Mascali JJ, Grady SR et al (1984) Involvement of cell–cell adhesion molecules in liver colonization by metastatic murine lymphoma/lymphosarcoma variants. Clin Exp Metastasis 2(3):213–222PubMedCrossRef

10.

Tabaries S, Dong Z, Annis MG et al (2011) Claudin-2 is selectively enriched in and promotes the formation of breast cancer liver metastases through engagement of integrin complexes. Oncogene 30(11):1318–1328

11.

Mannori G, Crottet P, Cecconi O et al (1995) Differential colon cancer cell adhesion to E-, P-, and L-selectin: role of mucin-type glycoproteins. Cancer Res 55(19):4425–4431PubMed

12.

Paschos KA, Canovas D, Bird NC (2009) The role of cell adhesion molecules in the progression of colorectal cancer and the development of liver metastasis. Cell Signal 21(5):665–674PubMedCrossRef

13.

Lou Y, Preobrazhenska O, auf dem Keller U et al (2008) Epithelial-mesenchymal transition (EMT) is not sufficient for spontaneous murine breast cancer metastasis. Dev Dyn 237(10):2755–2768PubMedCrossRef

14.

Aslakson CJ, Miller FR (1992) Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumor. Cancer Res 52(6):1399–1405PubMed

15.

Luebke-Wheeler JL, Nedredal G, Yee L et al (2009) E-cadherin protects primary hepatocyte spheroids from cell death by a caspase-independent mechanism. Cell Transplant 18(12):1281–1287PubMedCrossRef

16.

Lugo-Martinez VH, Petit CS, Fouquet S et al (2009) Epidermal growth factor receptor is involved in enterocyte anoikis through the dismantling of E-cadherin-mediated junctions. Am J Physiol Gastrointest Liver Physiol 296(2):G235–G244PubMedCrossRef

17.

Pece S, Chiariello M, Murga C et al (1999) Activation of the protein kinase Akt/PKB by the formation of E-cadherin-mediated cell–cell junctions. Evidence for the association of phosphatidylinositol 3-kinase with the E-cadherin adhesion complex. J Biol Chem 274(27):19347–19351PubMedCrossRef

18.

Pece S, Gutkind JS (2000) Signaling from E-cadherins to the MAPK pathway by the recruitment and activation of epidermal growth factor receptors upon cell–cell contact formation. J Biol Chem 275(52):41227–41233PubMedCrossRef

19.

Carmeliet P, Lampugnani MG, Moons L et al (1999) Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. Cell 98(2):147–157PubMedCrossRef

20.

Yates CC, Shepard CR, Stolz DB et al (2007) Co-culturing human prostate carcinoma cells with hepatocytes leads to increased expression of E-cadherin. Br J Cancer 96(8):1246–1252PubMedCrossRef

21.

Chao YL, Shepard CR, Wells A (2010) Breast carcinoma cells re-express E-cadherin during mesenchymal to epithelial reverting transition. Mol Cancer 9:179PubMedCrossRef

22.

Li M, Aliotta JM, Asara JM et al (2010) Intercellular transfer of proteins as identified by stable isotope labeling of amino acids in cell culture. J Biol Chem 285(9):6285–6297PubMedCrossRef

23.

St Croix B, Kerbel RS (1997) Cell adhesion and drug resistance in cancer. Curr Opin Oncol 9(6):549–556PubMedCrossRef

24.

Green SK, Francia G, Isidoro C et al (2004) Antiadhesive antibodies targeting E-cadherin sensitize multicellular tumor spheroids to chemotherapy in vitro. Mol Cancer Ther 3(2):149–159PubMed

25.

Wang L, Li Z, Wang C et al (2009) E-cadherin decreased human breast cancer cells sensitivity to staurosporine by up-regulating Bcl-2 expression. Arch Biochem Biophys 481(1):116–122PubMedCrossRef

26.

Yates C, Wells A, Turner T (2005) Luteinising hormone-releasing hormone analogue reverses the cell adhesion profile of EGFR overexpressing DU-145 human prostate carcinoma subline. Br J Cancer 92(2):366–375PubMed

27.

Guriec N, Marcellin L, Gairard B et al (1996) E-cadherin mRNA expression in breast carcinomas correlates with overall and disease-free survival. Invasion Metastasis 16(1):19–26PubMed

28.

Brown LA, Arterburn LM, Miller AP et al (2003) Maintenance of liver functions in rat hepatocytes cultured as spheroids in a rotating wall vessel. In Vitro Cell Dev Biol Anim 39(1–2):13–20PubMedCrossRef

29.

Dash A, Inman W, Hoffmaster K et al (2009) Liver tissue engineering in the evaluation of drug safety. Expert Opin Drug Metab Toxicol 5(10):1159–1174PubMedCrossRef

30.

Powers MJ, Domansky K, Kaazempur-Mofrad MR et al (2002) A microfabricated array bioreactor for perfused 3D liver culture. Biotechnol Bioeng 78(3):257–269PubMedCrossRef

31.

Gassmann P, Haier J (2008) The tumor cell–host organ interface in the early onset of metastatic organ colonisation. Clin Exp Metastasis 25(2):171–181PubMedCrossRef

32.

Chao YL, Wu Q, Acquafondata M et al (2011) Partial mesenchymal to epithelial reverting transition in breast and prostate cancer metastases [abstract nr. 3357]. In: Proceedings of the 102nd annual meeting of the American Association for Cancer Research. Orlando, FL, Philadelphia (PA): AACR

33.

Bergin E, Levine JS, Koh JS et al (2000) Mouse proximal tubular cell–cell adhesion inhibits apoptosis by a cadherin-dependent mechanism. Am J Physiol Renal Physiol 278(5):F758–F768PubMed

34.

Langley RR, Fan D, Guo L et al (2009) Generation of an immortalized astrocyte cell line from H-2Kb-tsA58 mice to study the role of astrocytes in brain metastasis. Int J Oncol 35(4):665–672PubMedCrossRef

35.

Lin Q, Balasubramanian K, Fan D et al (2010) Reactive astrocytes protect melanoma cells from chemotherapy by sequestering intracellular calcium through gap junction communication channels. Neoplasia 12(9):748–754PubMed

36.

West KA, Castillo SS, Dennis PA (2002) Activation of the PI3K/Akt pathway and chemotherapeutic resistance. Drug Resist Updat 5(6):234–248PubMedCrossRef

37.

St Croix B, Florenes VA, Rak JW et al (1996) Impact of the cyclin-dependent kinase inhibitor p27Kip1 on resistance of tumor cells to anticancer agents. Nat Med 2(11):1204–1210PubMedCrossRef

38.

St Croix B, Sheehan C, Rak JW et al (1998) E-Cadherin-dependent growth suppression is mediated by the cyclin-dependent kinase inhibitor p27 (KIP1). J Cell Biol 142(2):557–571PubMedCrossRef

39.

Li Z, Zhou Z, Donahue HJ (2008) Alterations in Cx43 and OB-cadherin affect breast cancer cell metastatic potential. Clin Exp Metastasis 25(3):265–272PubMedCrossRef

40.

Chu K, Cheng CJ, Ye X et al (2008) Cadherin-11 promotes the metastasis of prostate cancer cells to bone. Mol Cancer Res 6(8):1259–1267PubMedCrossRef

41.

Tsuji T, Ibaragi S, Hu GF (2009) Epithelial-mesenchymal transition and cell cooperativity in metastasis. Cancer Res 69(18):7135–7139PubMedCrossRef

Title: Hepatocyte induced re-expression of E-cadherin in breast and prostate cancer cells increases chemoresistance
Authors: Yvonne Chao
Qian Wu
Christopher Shepard
Alan Wells
Publication date: 01-01-2012
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 1/2012
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-011-9427-3

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