Introduction

The genetic changes that promote progression of prostate adenocarcinomas are multifactori-al and include alterations in several genes. The aberrations include those in genes that affect normal cell adhesion. The long arm of chromosome 16 (16q22.1) is deleted in 30% of primary prostatic tumors and more than 70% of metastatic prostate cancers. The E-cadherin gene is located in this region. E-cadherin is involved in maintaining homotypic cell-cell adhesion between normal prostatic glandular cells. The loss of E-cadherin expression is associated with metastatic progression of prostate cancer (Mason, 2002). Recent data suggests that abnormal expression of E-cadherin, leading to impaired adhesion, correlates with hematoge-nous spread of primary tumor cells in prostate cancer patients (Loric, 2001). The study further suggests that abnormal E-cadherin expression is a significant independent indicator of prostate cancer recurrence in patients.

Metastatic dissemination of prostate cancer cells occurs via the lymphatic system as well as the vascular system. This complex process of metastasis involves a series of steps starting with neoplastic transformation of prostate cells, tumor angiogenesis/lymphogenesis and cancer growth, loss of cell adhesion molecules and detachment of cancer cells from primary tumor, local invasion of stroma, dissemination of primary tumor cells via the lymphatics or vasculature, avoidance of tumor surveillance by the immune system, homing of primary prostate cancer cells to distant sites, establishment of tumor and growth of tumor at distant metastatic site (Arya et al., 2006). While the majority of metastic lesions are found in the obturator lymph nodes, lesions have also been detected in presacral, presciatic, as well as internal and external iliac nodes. Conversely, hematogenous spread of prostate cancer cells results in the formation of metastatic lesions in the bone, lung, liver and epidural space. Interestingly, in the majority of patients who die from prostate cancer, metastatic lesions have been detected in the bone. One study shows that E-cadherin and p-catenin are downregulat-ed in prostatic bone metastasis, but not in primary prostate tumors (Arya et al., 2006). The spine, femur, pelvis, rib cage, skull and humerus are frequent sites of metastatic prostate cancer lesions. The bone stroma apparently provides a microenvironment suitable for the growth of metastatic prostate cancer cells. While the molecular mechanisms associated with prostate cancer metastasis are not completely elucidated, potential markers of high-risk prostate cancer include the cadherins, catenins, focal adhesin kinase, connexins, integrins and metalloproteinases (Mol et al., 2007).

The E-cadherin-catenin complex and associated proteins have functional roles in cell-adhesion as well as in downstream signaling. It is well known that increased expression of cyto-plasmic p-catenin is associated with increased translocation to the nucleus leading to transcriptional activation of p-catenin-TCF responsive genes. p-catenin, y-catenin and p120ctn proteins are expressed in the nucleus, thereby suggesting that a complex system of checks and balances may exist in normal as well as in tumor cells.

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