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Clinical and Biological Significance of KISS1 Expression in Prostate Cancer
Honghe Wang,* Jacqueline Jones,* Timothy Turner,* Qinghua P. He,† Shana Hardy,* William E. Grizzle,‡ Danny R. Welch,§ and Clayton Yates*
From the Departments of Biology and Center for Cancer Research* and Chemical Engineering,† Tuskegee University, Tuskegee, Alabama; the Department of Pathology,‡ School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and the Department of Cancer Biology,§ University of Kansas Medical Center, Kansas City, Kansas
The American Journal of Pathology, Vol. 180, Issue 3, Pages 1170-1178, March 2012, DOI: 10.1016/j.ajpath.2011.11.020
Prostate cancer (PCa) is the most frequent malignancy and the second leading cause of cancer mortality in men. Although early detection and hormone-based therapies generally result in a reduction of mortalities rate, current therapies for advanced or recurrent PCa are not curative. Since metastasis is responsible for most the deaths, the Yates lab sought to investigate potential factors that may play a role in aiding in PCa progression.
One protein under current investigation in the Yates lab is KISS1. The KISS1 gene was first identified as a metastasis suppressor for human melanoma. Although KISS1 functions as a metastasis suppressor in various cancers, its expression levels and functions in PCa remain undetermined. The goals of this study were to determine the clinicopathological characteristics of KISS1 during PCa progression.
Strong detectable KISS1 staining was observed in benign prostate tissues; however, low intensity of KISS1 expression was found in primary and metastatic PCas (both P < 0.001, t-test). Furthermore, the low expression levels of KISS1 in PCas correlated with clinical stage (P < 0.01) and with KISS1R expression (P < 0.001). Overexpression of full-length KISS1 in low KISS1-expressing PC-3M cells, but not KFMΔSS, which lacks the secretion signal sequence, induced re-sensitization of cells to anoikis, although it had no effect on either cell proliferation or apoptosis. Overexpression of KISS1 also suppressed steps in the metastatic cascade, including motility and invasiveness. Moreover, cells overexpressing KISS1 were found to enhance chemosensitivity to paclitaxel.
Collectively, these results indicate that loss of KISS1 expression in PCas is associated with increased cancer progression and KISS1 regulates steps that are involved in cell metastasis. The Yates lab data strongly suggest that KISS1 functions as a metastasis suppressor in PCas and may serve as a useful biomarker as well as a therapeutic target for aggressive PCas.