Preferential production of latent transforming growth factor β-2 by primary prostatic epithelial cells and its activation by prostate-specific antigen

S. L. Dallas, S. Zhao, S. D. Cramer, Z. Chen, D. M. Peehl, Lynda Bonewald

Research output: Contribution to journalArticle

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Abstract

Three mammalian isoforms of transforming growth factor-β (TGFβ) are known, TGFβ1, 2, and 3, that have non-overlapping functions during development. However, their specific roles in cancers such as prostate cancer are less clear. Here we show that primary cultures of prostatic epithelial cells preferentially produce and activate the latent TGFβ2 isoform. Paired cultures of normal and malignant prostate cells from prostate cancer patients produced predominantly the TGFβ2 isoform, with 30- to 70-fold less TGFβ1. By mono-Q ion exchange chromatography, three major peaks of latent TGFβ2 activity were observed corresponding to the known small latent TGFβ2 complex, the known large latent TGFβ2 complex and a novel eluting peak of latent TGFβ2. Although prostate cells are known to activate latent TGFβ, the mechanism for activation is currently unclear. We investigated whether prostate specific antigen (PSA), a serine protease used as a clinical marker for prostate cancer, could play a role in the activation of latent TGFβ. Unlike plasmin, a known activator of both latent TGFβ1 and 2, PSA specifically activated the recombinant small latent form of TGFβ2, but not TGFβ1. Prostate epithelial cells, therefore, preferentially produce the TGFβ2 isoform and PSA, a protease produced by the prostate, specifically targets the activation of this TGFβ isoform. PSA-mediated activation of latent TGFβ2 may be an important mechanism for autocrine TGFβ regulation in the prostate and may potentially contribute to the formation of osteoblastic lesions in bone metastatic prostate cancer.

Original languageEnglish (US)
Pages (from-to)361-370
Number of pages10
JournalJournal of Cellular Physiology
Volume202
Issue number2
DOIs
StatePublished - Feb 2005
Externally publishedYes

Fingerprint

Transforming Growth Factors
Prostate-Specific Antigen
Prostate
Protein Isoforms
Epithelial Cells
Chemical activation
Prostatic Neoplasms
Fibrinolysin
Ion Exchange Chromatography
Serine Proteases
Chromatography
Ion exchange
Bone
Peptide Hydrolases
Biomarkers
Bone and Bones
Neoplasms

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Preferential production of latent transforming growth factor β-2 by primary prostatic epithelial cells and its activation by prostate-specific antigen. / Dallas, S. L.; Zhao, S.; Cramer, S. D.; Chen, Z.; Peehl, D. M.; Bonewald, Lynda.

In: Journal of Cellular Physiology, Vol. 202, No. 2, 02.2005, p. 361-370.

Research output: Contribution to journalArticle

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