Cadherin-23 Mediates Heterotypic Cell-cell Adhesion Between Breast Cancer Epithelial Cells and Fibroblasts

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Mar 14

PMID 22413011

Citations 25

Authors

Maria Apostolopoulou

Lee Ligon

Affiliations

Soon will be listed here.

Abstract

In the early stages of breast cancer metastasis, epithelial cells penetrate the basement membrane and invade the surrounding stroma, where they encounter fibroblasts. Paracrine signaling between fibroblasts and epithelial tumor cells contributes to the metastatic cascade, but little is known about the role of adhesive contacts between these two cell types in metastasis. Here we show that MCF-7 breast cancer epithelial cells and normal breast fibroblasts form heterotypic adhesions when grown together in co-culture, as evidenced by adhesion assays. PCR and immunoblotting show that both cell types express multiple members of the cadherin superfamily, including the atypical cadherin, cadherin-23, when grown in isolation and in co-culture. Immunocytochemistry experiments show that cadherin-23 localizes to homotypic adhesions between MCF-7 cells and also to heterotypic adhesions between the epithelial cells and fibroblasts, and antibody inhibition and RNAi experiments show that cadherin-23 plays a role in mediating these adhesive interactions. Finally, we show that cadherin-23 is upregulated in breast cancer tissue samples, and we hypothesize that heterotypic adhesions mediated by this atypical cadherin may play a role in the early stages of metastasis.

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References

Wadlow R, Wittner B, Finley S, Bergquist H, Upadhyay R, Finn S . Systems-level modeling of cancer-fibroblast interaction. PLoS One. 2009; 4(9):e6888. PMC: 2731225. DOI: 10.1371/journal.pone.0006888. View

Sakaguchi H, Tokita J, Muller U, Kachar B . Tip links in hair cells: molecular composition and role in hearing loss. Curr Opin Otolaryngol Head Neck Surg. 2009; 17(5):388-93. PMC: 2921850. DOI: 10.1097/MOO.0b013e3283303472. View

Kazmierczak P, Sakaguchi H, Tokita J, Wilson-Kubalek E, Milligan R, Muller U . Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells. Nature. 2007; 449(7158):87-91. DOI: 10.1038/nature06091. View

Elledge H, Kazmierczak P, Clark P, Joseph J, Kolatkar A, Kuhn P . Structure of the N terminus of cadherin 23 reveals a new adhesion mechanism for a subset of cadherin superfamily members. Proc Natl Acad Sci U S A. 2010; 107(23):10708-12. PMC: 2890781. DOI: 10.1073/pnas.1006284107. View

Smalley K, Brafford P, Haass N, Brandner J, Brown E, Herlyn M . Up-regulated expression of zonula occludens protein-1 in human melanoma associates with N-cadherin and contributes to invasion and adhesion. Am J Pathol. 2005; 166(5):1541-54. PMC: 1606406. DOI: 10.1016/S0002-9440(10)62370-X. View

Nieman M, Prudoff R, Johnson K, Wheelock M . N-cadherin promotes motility in human breast cancer cells regardless of their E-cadherin expression. J Cell Biol. 1999; 147(3):631-44. PMC: 2151177. DOI: 10.1083/jcb.147.3.631. View

Taniuchi K, Nakagawa H, Hosokawa M, Nakamura T, Eguchi H, Ohigashi H . Overexpressed P-cadherin/CDH3 promotes motility of pancreatic cancer cells by interacting with p120ctn and activating rho-family GTPases. Cancer Res. 2005; 65(8):3092-9. DOI: 10.1158/0008.5472.CAN-04-3646. View

Yonezawa S, Yoshizaki N, Kageyama T, Takahashi T, Sano M, Tokita Y . Fates of Cdh23/CDH23 with mutations affecting the cytoplasmic region. Hum Mutat. 2005; 27(1):88-97. DOI: 10.1002/humu.20266. View

Hirano S, Suzuki S, Redies C . The cadherin superfamily in neural development: diversity, function and interaction with other molecules. Front Biosci. 2002; 8:d306-55. DOI: 10.2741/972. View

10.

Lagziel A, Ahmed Z, Schultz J, Morell R, Belyantseva I, Friedman T . Spatiotemporal pattern and isoforms of cadherin 23 in wild type and waltzer mice during inner ear hair cell development. Dev Biol. 2005; 280(2):295-306. DOI: 10.1016/j.ydbio.2005.01.015. View

11.

Grusche F, Richardson H, Harvey K . Upstream regulation of the hippo size control pathway. Curr Biol. 2010; 20(13):R574-82. DOI: 10.1016/j.cub.2010.05.023. View

12.

Kang H, Jenabi J, Zhang J, Keshelava N, Shimada H, May W . E-cadherin cell-cell adhesion in ewing tumor cells mediates suppression of anoikis through activation of the ErbB4 tyrosine kinase. Cancer Res. 2007; 67(7):3094-105. PMC: 3906735. DOI: 10.1158/0008-5472.CAN-06-3259. View

13.

Moll R, Franke W, Schiller D, Geiger B, Krepler R . The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell. 1982; 31(1):11-24. DOI: 10.1016/0092-8674(82)90400-7. View

14.

Omelchenko T, Fetisova E, Ivanova O, Bonder E, Feder H, Vasiliev J . Contact interactions between epitheliocytes and fibroblasts: formation of heterotypic cadherin-containing adhesion sites is accompanied by local cytoskeletal reorganization. Proc Natl Acad Sci U S A. 2001; 98(15):8632-7. PMC: 37487. DOI: 10.1073/pnas.151247698. View

15.

Sotomayor M, Weihofen W, Gaudet R, Corey D . Structural determinants of cadherin-23 function in hearing and deafness. Neuron. 2010; 66(1):85-100. PMC: 2948466. DOI: 10.1016/j.neuron.2010.03.028. View

16.

Feltes C, Kudo A, Blaschuk O, Byers S . An alternatively spliced cadherin-11 enhances human breast cancer cell invasion. Cancer Res. 2002; 62(22):6688-97. View

17.

Bolz H, von Brederlow B, Ramirez A, Bryda E, Kutsche K, Nothwang H . Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D. Nat Genet. 2001; 27(1):108-12. DOI: 10.1038/83667. View

18.

Masur K, Lang K, Niggemann B, Zanker K, Entschladen F . High PKC alpha and low E-cadherin expression contribute to high migratory activity of colon carcinoma cells. Mol Biol Cell. 2001; 12(7):1973-82. PMC: 55643. DOI: 10.1091/mbc.12.7.1973. View

19.

Tanoue T, Takeichi M . New insights into Fat cadherins. J Cell Sci. 2005; 118(Pt 11):2347-53. DOI: 10.1242/jcs.02398. View

20.

Hulpiau P, van Roy F . Molecular evolution of the cadherin superfamily. Int J Biochem Cell Biol. 2008; 41(2):349-69. DOI: 10.1016/j.biocel.2008.09.027. View