The Cell Biology of CD44 in the Normal and Neoplastic Prostate In Vivo and In Vitro
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In collaboration with David L.
Cooper, Ph.D., M.D. we are studying the role of CD44 in
the normal, preneoplastic and
neoplastic prostate cells in vivo and in vitro. CD44 is a HCAM
(Hyaluronan Cell Adhesion Molecule) that has been linked to tumor
growth and metastasis in both human and rodent cancers. Previous
work by our group has indicated that human colonic
adenocarcinomas expressing alternatively spliced variant isoforms
of CD44 were associated with an unfavorable prognosis. In
prostate, CD44 expression had been identified in cancerous cell
lines at m-RNA level and in normal tissues by immunohistochemical
methods. However, a description of the m-RNA and protein
expression is still lacking. Data from our laboratory indicates
that expression of CD44 standard (CD44s) and its alternately
spliced isoform variants (CD44v) are decreased in adenocarcinomas
of the prostate. It is our intent to study metastatic prostate
cancers and CD44 isoform expression. We propose that metastatic
potential could be conferred on prostate cancers by loss of
expression of CD44 and its isoforms. We intend to study CD44 and PSA levels in serum of patients with prostate cancer, using ELISA and CE LIF-ID. Preliminary data from our laboratory suggests shedding of CD44 from prostate cells during establishment in cell cultures. Decreased expression of CD44 and variants on prostate cancer cells could be a consequence of shedding from the cell surface. We speculate that CD44 and PSA levels together would be more specific in detecting prostate cancer. We will also evaluate the factors controlling the expression of CD44 in primary cultures of normal and neoplastic prostate epithelial cells. We have successfully expanded primary cultures of both normal and neoplastic cells from radical prostatectomy specimens. We already have preliminary data on these cell lines using RT-PCR, Western blotting and immuno-fluorescence. We intend to study methylation of the CD44 gene to see if it could account for the loss of CD44 expression in metastatic disease of the prostate. |
