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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.
Am J Pathol 2010; 176(6):2986-96AJ

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+Show Affiliations

Greenebaum Cancer Center, University of Maryland Baltimore, Baltimore, MD 21201, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20382709

Citation

Chen, Ya-Wen, et al. "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." The American Journal of Pathology, vol. 176, no. 6, 2010, pp. 2986-96.
Chen YW, Lee MS, Lucht A, et al. 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. Am J Pathol. 2010;176(6):2986-96.
Chen, Y. W., Lee, M. S., Lucht, A., Chou, F. P., Huang, W., Havighurst, T. C., ... Lin, C. Y. (2010). 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. The American Journal of Pathology, 176(6), pp. 2986-96. doi:10.2353/ajpath.2010.090665.
Chen YW, et al. 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. Am J Pathol. 2010;176(6):2986-96. PubMed PMID: 20382709.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Chen,Ya-Wen, AU - Lee,Ming-Shyue, AU - Lucht,Amanda, AU - Chou,Feng-Pai, AU - Huang,Wei, AU - Havighurst,Thomas C, AU - Kim,KyungMann, AU - Wang,Jehng-Kang, AU - Antalis,Toni M, AU - Johnson,Michael D, AU - Lin,Chen-Yong, Y1 - 2010/04/09/ PY - 2010/4/13/entrez PY - 2010/4/13/pubmed PY - 2010/10/5/medline SP - 2986 EP - 96 JF - The American journal of pathology JO - Am. J. Pathol. VL - 176 IS - 6 N2 - 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. SN - 1525-2191 UR - https://www.unboundmedicine.com/medline/citation/20382709/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9440(10)60818-8 DB - PRIME DP - Unbound Medicine ER -