Clinical and biological significance of KISS1 expression in prostate cancer.
For men in the United States, prostate cancer (PCa) is the most frequent malignancy and the second leading cause of cancer mortality. The metastatic spread of PCa is responsible for most deaths related to PCa. Although KISS1 functions as a metastasis suppressor in various cancers, its expression levels and functions in PCa development and progression remain undetermined. The goals of this study were to correlate the expression levels of KISS1 in PCas with clinicopathologic characteristics and to assess the biological relevance of KISS1 to the viability and motility of PCa cells. Strong KISS1 staining was detected in benign prostate tissues, but the staining was weaker 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, our data 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.
Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, Alabama. Electronic address: wangh@mytu.tuskegee.edu.
Honghe
H
Wang
Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, Alabama.
Jacqueline
J
Jones
Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, Alabama.
Timothy
T
Turner
Department of Chemical Engineering, Tuskegee University, Tuskegee, Alabama.
Qinghua P
QP
He
Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, Alabama.
Shana
S
Hardy
Department of Pathology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
William E
WE
Grizzle
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, Kansas.
Danny R
DR
Welch
Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, Alabama. Electronic address: cyates@mytu.tuskegee.edu.
Clayton
C
Yates
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D059648:Kisspeptins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C106628:KISS1 protein, human; D059648:Kisspeptins