Classical Cadherins Type II 51 Cadherin

Type II cadherins, cadherins 5, 6, 7, 8, 9, 10, 11, and 12, have structural features similar to Type I cadherins, but differ in amino acid sequence. Type II mesenchymal cadherins are normally expressed on stromal cells and osteoblasts. A mesenchymal cadherin, cadherin 11, and its truncated variant are expressed on highly invasive breast cancer cell lines (Pishvaian et al., 1999), but not on non-invasive cell lines. Previous studies have shown that cadherin 11 is expressed in embryonic mesenchymal tissues, and restricted to certain regions of neural tube (Kimura et al., 1995; Hoffman and Balling, 1995). As tumor cells become more invasive and less differentiated, with concomitant loss of E-cadherin expression, there is an increase in mesenchymal cadherin expression. This pattern would suggest an epithelial to mesenchymal transition of highly invasive, poorly differentiated tumor cells. Although little is known about the expression pattern and function of Type II cadherins in prostate cancer cell lines, expression of cadherin 11 may facilitate metastasis of cancer cells and form distant lesions, particularly in the bone (Bussemakers et al., 2000; Tomita et al., 2000). It is important to note that patients with advanced lung, breast or prostate cancers develop bone metastasis (Mundy, 2002; Soos et al., 1997). In humans, prostate cancer cells invade Batson's vertebral veins, allowing metastatic cancer cells to reach and colonize distant sites within the bone (Geldof, 1997; Oesterling et al, 1997; Lehr and Pienta, 1998). Therefore, successive E-cadherin down-regulation, expression of metalloproteinases, and expression of mesenchymal cadherins allow prostate cancer cells to follow a defined metastatic pathway. The prostate cancer cells may disassociate, invade the basement membrane, metasta-size, and colonize distant sites in the bone with concomitant expression of mesenchymal cadherin 11. This type of cancer cell-stromal cell interaction mediated by cadherin 11 is seen in invasive gastric cancers (Shibata et al., 1996). It is possible that E-cadherin acts as a tumor suppressor in cancer progression, while cadherin 11 regulates invasion and formation of metastatic lesions in the bone. This would warrant further investigation of the expression pattern and function of cadherin 11, as well as its role in signalling metastatic progression of prostate cancer cell lines.

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