Prostate-specific antigen (PSA) is an insulin-like growth factor binding protein-3 protease found in seminal plasma.

Cohen, Pinchas; Graves, Howard C.B.; Peehl, Donna M.; Kamarei, Mehdi; Giudice, Linda C.; Rosenfeld, Ron G.

doi:10.1210/jcem.75.4.1383255

Cited by 250 publications

(212 citation statements)

References 27 publications

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“…Bands of approximately 43, 37, 33, 25, and 23 kd were found and appeared to correspond to the molecular weight described for the IGFBP (25,26). On the other hand, although the first 2 bands correspond to the IGFBP-3 doublet, the others might represent degradation products of the latter (26,27). Characterization of these bands is under way.…”

Section: Expression Of Type 1 Igf Receptormentioning

confidence: 80%

Human Osteoarthritic Chondrocytes Possess an Increased Number of Insulin‐Like Growth Factor 1 Binding Sites but are Unresponsive to its Stimulation

Doré

Pelletier

DiBattista

et al. 1994

Arthritis & Rheumatism

186

117

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Objective. To characterize the insulin-like growth factor 1 (IGF-1) receptor in human osteoarthritic (OA) and normal adult chondrocytes. The biologic response of chondrocytes to IGF-1 stimulation was examined, as was the presence and synthesis of IGF binding proteins (IGFBP) in these cells.Methods. Binding studies, Northern blot, immunohistochemical analysis, and affinity cross-linking experiments were performed for characterization of the IGF receptor, and the latter method was also used for IGFBP determination. The biologic response was estimated via the incorporation of radiolabeled proline into a newly synthesized protein.Results histochemical studies with a monoclonal antibody (MAb) against the type 1 IGF receptor (aIR3) showed increased staining in OA cartilage compared with normal tissue. Biologic responses of chondrocytes after IGF-1 stimulation revealed that OA chondrocytes were unresponsive, whereas a 2.5-fold increase in new protein synthesis was observed in normal cells. Competition studies in normal chondrocytes revealed that both IGF-1 and IGF-2 displaced radiolabeled IGF-1 in a comparable manner; however, insulin at high concentration weakly competes. Moreover, MAb aIR3 effectively blocked specific binding in normal chondrocytes (77 %), but not in OA chondrocytes (26%). Northern blot and covalent cross-linking analyses revealed the specific band characteristic of type 1 receptor. With the latter technique, other bands corresponding to the IGFBPs were also detected. Comparison between normal and OA chondrocytes showed increased intensity of the IGFBP bands, particularly those corresponding to the IGFBP-3 doublet.Conclusion. It is shown that type 1 IGF receptor is expressed in human articular cartilage and that the level of binding sites is significantly increased in OA chondrocytes. Interestingly, despite the higher level of binding sites in OA cells, no response to IGF-1 stimulation was found in these cells. Our data suggest that this increase in specific binding may involve not only the type 1 IGF receptor but also IGFBP on the cell surface. The latter, by binding the IGF-1, will diminish the bioavailability of IGF-1 and thus prevent its anabolic action.Osteoarthritis (OA) is the most common of the various arthritic disorders affecting humans. The dis-

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Section: Expression Of Type 1 Igf Receptormentioning

confidence: 80%

Human Osteoarthritic Chondrocytes Possess an Increased Number of Insulin‐Like Growth Factor 1 Binding Sites but are Unresponsive to its Stimulation

Doré

Pelletier

DiBattista

et al. 1994

Arthritis & Rheumatism

186

117

View full text Add to dashboard Cite

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“…hK3 has also been reported to cleave insulin-like growth factor-binding protein-3, resulting in increased availability of insulin-like growth factor. This suggests that hK3 enzymatic activity may promote proliferation, migration, and metastasis of prostate cancer cells (Cohen et al, 1992). It will be of interest to determine the functions and the potential of serum biomarker development for the other members of the kallikrein family.…”

mentioning

confidence: 99%

Characterisation of human kallikrein 6/protease M expression in ovarian cancer

Zhang

Huang

et al. 2004

Br J Cancer

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Kallikrein 6 (hK6, also known as protease M/zyme/neurosin) is a member of the human kallikrein gene family. We have previously cloned the cDNA for this gene by differential display and shown the overexpression of the mRNA in breast and ovarian primary tumour tissues and cell lines. To thoroughly characterise the expression of this kallikrein in ovarian cancer, we have developed a novel monoclonal antibody specific to hK6 and employed it in immunohistochemistry with a wide range of ovarian tumour samples. The expression was found elevated in 67 of 80 cases of ovarian tumour samples and there was a significant difference in the expression levels between normal and benign ovarian tissues and the borderline and invasive tumours (Po0.001). There was no difference of expression level between different subtypes of tumours. More significantly, high level of kallikrein 6 expression was found in many early-stage and low-grade tumours, and elevated hK6 proteins were found in benign epithelia coexisting with borderline and invasive tissues, suggesting that overexpression of hK6 is an early phenomenon in the development of ovarian cancer. Quantitative real-time reverse transcription -polymerase chain reactions also showed elevated kallikrein 6 mRNA expression in ovarian tumours. Genomic Southern analysis of 19 ovarian tumour samples suggested that gene amplification is one mechanism for the overexpression of hK6 in ovarian cancer.

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“…Similarly, PSA has been shown to cleave cytokine binding proteins (such as insulin-like growth factor binding protein) directly, releasing cytokines, such as insulin-like growth factor-1, that are involved in growth stimulation and inflammation (Cohen et al, 1992;Platz et al, 2005). Additional evidence suggests that PSA may have a significant role in osteoblastic bone metastasis (Nelson et al, 1995;Shah et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

PSA reduces prostate cancer cell motility by stimulating TRPM8 activity and plasma membrane expression

et al. 2010

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Although the transient receptor potential melastatin 8 (TRPM8) cold receptor is highly expressed in prostate cancer (PCa) and constitutes a promising diagnostic and prognostic indicator, the natural agonists of this channel in the prostate, as well as its physiological and pathological functions, remain unknown. In this study, we identified the well-known PCa marker, prostatespecific antigen (PSA), as a physiological TRPM8 agonist. Electrophysiological and Ca 2 þ imaging studies demonstrated that PSA activated TRPM8-mediated current by the bradykinin 2 receptor signaling pathway. Further investigation of this mechanism by cell-surface biotinylation revealed that the increase in TRPM8 current induced by PSA was due to an increase in the number of functional TRPM8 channels on the plasma membrane. Importantly, wound-healing and migration assays revealed that TRPM8 activation by PSA reduced motility of the PC3 PCa cell line, suggesting that plasma membrane TRPM8 has a protective role in PCa progression. Consequently, PSA was identified as a natural TRPM8 agonist in the prostate and we propose a putative physiological role for both of these proteins in carcinogenesis, making this pathway a potentially important target for anticancer agent development.

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Prostate-specific antigen (PSA) is an insulin-like growth factor binding protein-3 protease found in seminal plasma.

Cited by 250 publications

References 27 publications

Human Osteoarthritic Chondrocytes Possess an Increased Number of Insulin‐Like Growth Factor 1 Binding Sites but are Unresponsive to its Stimulation

Human Osteoarthritic Chondrocytes Possess an Increased Number of Insulin‐Like Growth Factor 1 Binding Sites but are Unresponsive to its Stimulation

Characterisation of human kallikrein 6/protease M expression in ovarian cancer

PSA reduces prostate cancer cell motility by stimulating TRPM8 activity and plasma membrane expression

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