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The membrane-anchored serine protease, TMPRSS2, activates PAR-2 in prostate cancer cells.
Biochem J. 2005 Jun 15; 388(Pt 3):967-72.BJ

Abstract

TMPRSS2 is a type II transmembrane-bound serine protease that has gained interest owing to its highly localized expression in the prostate and its overexpression in neoplastic prostate epithelium. Once activated, the serine protease domain of TMPRSS2 is released from the cell surface into the extracellular space. PAR (protease-activated receptor)-2 belongs to a family of G-protein-coupled receptors (PAR-1-4) that are activated by specific serine proteases, which are expressed in many normal and malignant cell types. Previous in vitro studies on prostate cancer cells suggest a role for PAR-2 in prostate cancer metastasis. A polyclonal anti-human TMPRSS2 antibody was generated against the TMPRSS2 serine protease domain. The antibody showed specific reactivity with recombinant expressed TMPRSS2, and so was used to extract and purify the cleaved active TMPRSS2 protease from prostate cancer cells. Reverse transcriptase PCR and Western blot analysis were used to show the expression of both TMPRSS2 and PAR-2 in the androgen-dependent LNCaP prostate cancer cell line. Treatment of LNCaP cells with the cellular immunopurified TMPRSS2 protease induced a transient increase in intracellular calcium, which is indicative of G-protein-coupled-receptor activation. This calcium mobilization was inhibited by cellular pre-treatment with a specific PAR-2 antagonist, but not with a PAR-1 antagonist; inhibition of the protease activity also failed to mobilize calcium, suggesting that TMPRSS2 is capable of cleaving and thereby activating the PAR-2 receptor. The calcium mobilization was also inhibited by cellular pre-treatment with suramin or 2-APB (2-aminoethoxydiphenyl borate), indicating that a G-protein pathway is involved and that subsequent calcium release is mainly from intracellular stores. The present study describes how TMPRSS2 may contribute to prostate tumour metastasis via the activation of PAR-2.

Authors+Show Affiliations

School of Pharmacy, Medical Biology Centre, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.No 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, Non-U.S. Gov't

Language

eng

PubMed ID

15537383

Citation

Wilson, Susan, et al. "The Membrane-anchored Serine Protease, TMPRSS2, Activates PAR-2 in Prostate Cancer Cells." The Biochemical Journal, vol. 388, no. Pt 3, 2005, pp. 967-72.
Wilson S, Greer B, Hooper J, et al. The membrane-anchored serine protease, TMPRSS2, activates PAR-2 in prostate cancer cells. Biochem J. 2005;388(Pt 3):967-72.
Wilson, S., Greer, B., Hooper, J., Zijlstra, A., Walker, B., Quigley, J., & Hawthorne, S. (2005). The membrane-anchored serine protease, TMPRSS2, activates PAR-2 in prostate cancer cells. The Biochemical Journal, 388(Pt 3), 967-72.
Wilson S, et al. The Membrane-anchored Serine Protease, TMPRSS2, Activates PAR-2 in Prostate Cancer Cells. Biochem J. 2005 Jun 15;388(Pt 3):967-72. PubMed PMID: 15537383.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The membrane-anchored serine protease, TMPRSS2, activates PAR-2 in prostate cancer cells. AU - Wilson,Susan, AU - Greer,Brett, AU - Hooper,John, AU - Zijlstra,Andries, AU - Walker,Brian, AU - Quigley,James, AU - Hawthorne,Susan, PY - 2004/11/13/pubmed PY - 2005/12/15/medline PY - 2004/11/13/entrez SP - 967 EP - 72 JF - The Biochemical journal JO - Biochem. J. VL - 388 IS - Pt 3 N2 - TMPRSS2 is a type II transmembrane-bound serine protease that has gained interest owing to its highly localized expression in the prostate and its overexpression in neoplastic prostate epithelium. Once activated, the serine protease domain of TMPRSS2 is released from the cell surface into the extracellular space. PAR (protease-activated receptor)-2 belongs to a family of G-protein-coupled receptors (PAR-1-4) that are activated by specific serine proteases, which are expressed in many normal and malignant cell types. Previous in vitro studies on prostate cancer cells suggest a role for PAR-2 in prostate cancer metastasis. A polyclonal anti-human TMPRSS2 antibody was generated against the TMPRSS2 serine protease domain. The antibody showed specific reactivity with recombinant expressed TMPRSS2, and so was used to extract and purify the cleaved active TMPRSS2 protease from prostate cancer cells. Reverse transcriptase PCR and Western blot analysis were used to show the expression of both TMPRSS2 and PAR-2 in the androgen-dependent LNCaP prostate cancer cell line. Treatment of LNCaP cells with the cellular immunopurified TMPRSS2 protease induced a transient increase in intracellular calcium, which is indicative of G-protein-coupled-receptor activation. This calcium mobilization was inhibited by cellular pre-treatment with a specific PAR-2 antagonist, but not with a PAR-1 antagonist; inhibition of the protease activity also failed to mobilize calcium, suggesting that TMPRSS2 is capable of cleaving and thereby activating the PAR-2 receptor. The calcium mobilization was also inhibited by cellular pre-treatment with suramin or 2-APB (2-aminoethoxydiphenyl borate), indicating that a G-protein pathway is involved and that subsequent calcium release is mainly from intracellular stores. The present study describes how TMPRSS2 may contribute to prostate tumour metastasis via the activation of PAR-2. SN - 1470-8728 UR - https://www.unboundmedicine.com/medline/citation/15537383/The_membrane_anchored_serine_protease_TMPRSS2_activates_PAR_2_in_prostate_cancer_cells_ L2 - https://portlandpress.com/biochemj/article-lookup/doi/10.1042/BJ20041066 DB - PRIME DP - Unbound Medicine ER -