SPANXB2 and Prostate Cancer Progression
Final summary rept. 15 Sep 2012 - 14 Sep 2014
MICHIGAN UNIV ANN ARBOR
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A critical problem in prostate cancer is our inability to reliably distinguish indolent from aggressive disease. Recent evidence has implicated a class of genes, termed Cancer Testis Antigens CTA, in cancer progression. In preliminary studies, by crossing the CTA bank with a prostate cancer metastasis gene signature we attained from an orthotopical injection xenograft model, we postulated CTA SPANXB2 as a cancer metastasis related CTA. We observed that SPANXB2 is up-regulated in metastatic prostate cancer xenograft models and is induced upon exposure to stroma and stromal factors i.e., TGF- . We hypothesize that SPANX-B2 may be the key regulator of prostate cancer aggressive cell behavior and metastasis. In this report, for the first time, we illustrate that regulatory role of SPANXB2 in PC3 cells by using shRNA knockdown technique. Knockdown of SPANXB2 in PC3 cells significantly reduces prostate caner aggressiveness in vitro and in vivo. We confirm that stromal cells stimulate SPANXB2 expression and promote cell aggressiveness in prostate caner cells. We demonstrated that elevated TGF- 2 upon stromal cells co-culture induced SPANXB2 and enhance prostate cancer invasion and metastasis. Finally we find the SPANXB2 is associated with the reactive stromal accumulation in tumors and correlated to tumor metastasis and survival outcome in clinical patients. Our data may provide a potential therapeutic target to treat prostate cancer metastasis.
- Medicine and Medical Research