title: 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.
abstract: 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.
authors.affiliation: Greenebaum Cancer Center, University of Maryland Baltimore, Baltimore, MD 21201, USA.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Chen
authors.forename: Ming-Shyue
authors.initials: MS
authors.lastname: Lee
authors.forename: Amanda
authors.initials: A
authors.lastname: Lucht
authors.forename: Feng-Pai
authors.initials: FP
authors.lastname: Chou
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Havighurst
authors.forename: KyungMann
authors.initials: K
authors.lastname: Kim
authors.forename: Jehng-Kang
authors.initials: JK
authors.lastname: Wang
authors.forename: Toni M
authors.initials: TM
authors.lastname: Antalis
authors.forename: Michael D
authors.initials: MD
authors.lastname: Johnson
authors.forename: Chen-Yong
authors.initials: CY
authors.lastname: Lin
mesh_terms: 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*
chemical_list: D000911:Antibodies, Monoclonal; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human
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