Mechanisms of KAI1/CD82-Induced Prostate Cancer Metastasis
Final rept. 1 Feb 2008-31 Jul 2011
VAN ANDEL RESEARCH INSTITUTE GRAND RAPIDS MI
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Metastatic prostate cancer kills over 28,000 American men every year. The mechanisms that drive metastasis are poorly understood. We investigated the hypothesis that loss of the metastasis suppressor gene, CD82KAI1 in primary prostate tumors of genetically engineered mice would be sufficient to induce metastasis. While CD82 was sufficient to suppress metastasis of metastatic tumor cells lines and did so by repressing c-Met, the reverse was not true, i.e. loss of CD82 was not sufficient to induce metastasis. This was the case in at least two genetically engineered prostate cancer models. Ongoing studies in different models may yet prove otherwise. Our other hypothesis, that CD82 was suppressing c-Met and invasion through integrins, was proven invalid in these studies. Other tetraspanins that CD82 associates with, i.e. CD9 and CD151 were required to suppress c- Met, but not invasion. Thus, these two events must be occurring via different mechanisms. Nonetheless, we are finding several interesting phenotypes in the CD82 null mice which will shed additional light on CD82 function overall and be useful in developing new hypotheses about how CD82 functions as a metastasis suppressor.
- Anatomy and Physiology
- Medicine and Medical Research