Claudin-2 Promotes Breast Cancer Liver Metastasis by Facilitating Tumor Cell Interactions with Hepatocytes

被引:95
作者
Tabaries, Sebastien [1 ,2 ]
Dupuy, Fanny [1 ,3 ]
Dong, Zhifeng [1 ,2 ]
Monast, Anie [1 ,2 ]
Annis, Matthew G. [1 ,2 ]
Spicer, Jonathan [4 ]
Ferri, Lorenzo E. [4 ]
Omeroglu, Atilla [5 ]
Basik, Mark [6 ]
Amir, Eitan [7 ,8 ]
Clemons, Mark [9 ]
Siegel, Peter M. [1 ,2 ,3 ]
机构
[1] McGill Univ, Goodman Canc Res Ctr, Montreal, PQ, Canada
[2] McGill Univ, Dept Med, Montreal, PQ, Canada
[3] McGill Univ, Dept Biochem, Montreal, PQ, Canada
[4] McGill Univ Hlth Ctr, Dept Surg, Montreal, PQ, Canada
[5] McGill Univ Hlth Ctr, Dept Pathol, Montreal, PQ, Canada
[6] Sir Mortimer B Davis Jewish Hosp, Segal Canc Ctr, Montreal, PQ, Canada
[7] Univ Toronto, Div Med Oncol, Toronto, ON, Canada
[8] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada
[9] Ottawa Hosp Canc Ctr, Div Med Oncol, Ottawa, ON, Canada
关键词
MAMMARY-CARCINOMA CELLS; HUMAN OVARIAN-CANCER; TIGHT JUNCTION; E-CADHERIN; EXPRESSION; TRANSITIONS; ACTIVATION; ADHESION; DISEASE; PROTEIN;
D O I
10.1128/MCB.00299-12
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We previously identified claudin-2 as a functional mediator of breast cancer liver metastasis. We now confirm that claudin-2 levels are elevated in liver metastases, but not in skin metastases, compared to levels in their matched primary tumors in patients with breast cancer. Moreover, claudin-2 is specifically expressed in liver-metastatic breast cancer cells compared to populations derived from bone or lung metastases. The increased liver tropism exhibited by claudin-2-expressing breast cancer cells requires claudin-2-mediated interactions between breast cancer cells and primary hepatocytes. Furthermore, the reduction of the claudin-2 expression level, either in cancer cells or in primary hepatocytes, diminishes these heterotypic cell-cell interactions. Finally, we demonstrate that the first claudin-2 extracellular loop is essential for mediating tumor cell-hepatocyte interactions and the ability of breast cancer cells to form liver metastases in vivo. Thus, during breast cancer liver metastasis, claudin-2 shifts from acting within tight-junctional complexes to functioning as an adhesion molecule between breast cancer cells and hepatocytes.
引用
收藏
页码:2979 / 2991
页数:13
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