TMPRSS2, a serine protease expressed in the prostate on the apical surface of luminal epithelial cells and released into semen in prostasomes, is misregulated in prostate cancer cells.
TMPRSS2, a type II transmembrane serine protease, is highly expressed by the epithelium of the human prostate gland. To explore the regulation and function of TMPRSS2 in the prostate, a panel of monoclonal antibodies with high sensitivity and specificity were generated. Immunodetection showed TMPRSS2 on the apical plasma membrane of the prostate luminal cells and demonstrated its release into semen as a component of prostasomes, organelle-like vesicles that may facilitate sperm function and enhance male reproduction. In prostate cancer cells, TMPRSS2 expression was increased and the protein mislocalized over the entire tumor cell membrane. In both LNCaP prostate cancer cells and human semen, TMPRSS2 protein was detected predominantly as inactive zymogen forms as part of an array of multiple noncovalent and disulfide-linked complexes, suggesting that TMPRSS2 activity may be regulated by unconventional mechanisms. Our data suggested that TMPRSS2, an apical surface serine protease, may have a normal role in male reproduction as a component of prostasomes. The aberrant cellular localization, and increased expression of the protease seen in cancer, may contribute to prostate tumorigenesis by providing access of the enzyme to nonphysiological substrates and binding-proteins.
Chen
Ya-Wen
YW
Greenebaum Cancer Center, University of Maryland Baltimore, Baltimore, MD 21201, USA.
Lee
Ming-Shyue
MS
Lucht
Amanda
A
Chou
Feng-Pai
FP
Huang
Wei
W
Havighurst
Thomas C
TC
Kim
KyungMann
K
Wang
Jehng-Kang
JK
Antalis
Toni M
TM
Johnson
Michael D
MD
Lin
Chen-Yong
CY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D046228:Microarray Analysis; D008875:Middle Aged; D011467:Prostate / Q000166:cytology* / Q000201:enzymology* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D012661:Semen / Q000201:enzymology*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human
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