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Receptor-mediated and protein kinase-dependent growth enhancement of primary human fibroblasts by platelet activating factor.
Mol Carcinog. 1997 Dec; 20(4):366-75.MC

Abstract

Chronic inflammation is a recognized risk factor for human cancer, but the causal mechanisms are poorly understood. We previously demonstrated that platelet activating factor (PAF) can induce alterations in the in vitro growth properties of primary rat fibroblasts. In the study reported here, exposure of primary human skin fibroblasts to PAF for 1 h in serum-free medium was shown to cause sustained proliferation over 50 d in medium containing low serum and anchorage-independent growth in soft agarose. Both properties could be inhibited by pretreatment with a PAF receptor antagonist, CV3988 (10 microM); a tyrosine-kinase inhibitor, genistein (1 microgram/mL); or a protein kinase C (PKC) inhibitor, staurosporine (50 nM) but not with a cyclooxygenase inhibitor, indomethacin (200 nM-20 microM). PAF had no effect on doubling time, saturation density, or cell viability under normal monolayer growth conditions in complete medium. Treatment with lyso-PAF, an inactive metabolite of PAF, had no effect in either of the assays. Control and PAF-induced cell proliferation in low-serum medium was inhibited by PAF receptor antagonists present during the extended growth period. The presence of PAF receptor mRNA in human skin fibroblasts was demonstrated by reverse transcriptase-polymerase chain reaction. The presence of a functional receptor was indicated by an early (2 min) transient increase in PKC activity and an increase in fos mRNA after PAF treatment. PAF-induced PKC activity was blocked by pretreatment with either staurosporine (50 nM) or CV3988 (1 microM). These results suggest that PAF is a mitogenic factor that contributes to the known increase in risk of malignancy associated with chronic inflammatory conditions.

Authors+Show Affiliations

Ottawa Regional Cancer Centre, Ontario, Canada.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9433481

Citation

Bennett, S A., and H C. Birnboim. "Receptor-mediated and Protein Kinase-dependent Growth Enhancement of Primary Human Fibroblasts By Platelet Activating Factor." Molecular Carcinogenesis, vol. 20, no. 4, 1997, pp. 366-75.
Bennett SA, Birnboim HC. Receptor-mediated and protein kinase-dependent growth enhancement of primary human fibroblasts by platelet activating factor. Mol Carcinog. 1997;20(4):366-75.
Bennett, S. A., & Birnboim, H. C. (1997). Receptor-mediated and protein kinase-dependent growth enhancement of primary human fibroblasts by platelet activating factor. Molecular Carcinogenesis, 20(4), 366-75.
Bennett SA, Birnboim HC. Receptor-mediated and Protein Kinase-dependent Growth Enhancement of Primary Human Fibroblasts By Platelet Activating Factor. Mol Carcinog. 1997;20(4):366-75. PubMed PMID: 9433481.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Receptor-mediated and protein kinase-dependent growth enhancement of primary human fibroblasts by platelet activating factor. AU - Bennett,S A, AU - Birnboim,H C, PY - 1998/1/20/pubmed PY - 2000/6/20/medline PY - 1998/1/20/entrez SP - 366 EP - 75 JF - Molecular carcinogenesis JO - Mol Carcinog VL - 20 IS - 4 N2 - Chronic inflammation is a recognized risk factor for human cancer, but the causal mechanisms are poorly understood. We previously demonstrated that platelet activating factor (PAF) can induce alterations in the in vitro growth properties of primary rat fibroblasts. In the study reported here, exposure of primary human skin fibroblasts to PAF for 1 h in serum-free medium was shown to cause sustained proliferation over 50 d in medium containing low serum and anchorage-independent growth in soft agarose. Both properties could be inhibited by pretreatment with a PAF receptor antagonist, CV3988 (10 microM); a tyrosine-kinase inhibitor, genistein (1 microgram/mL); or a protein kinase C (PKC) inhibitor, staurosporine (50 nM) but not with a cyclooxygenase inhibitor, indomethacin (200 nM-20 microM). PAF had no effect on doubling time, saturation density, or cell viability under normal monolayer growth conditions in complete medium. Treatment with lyso-PAF, an inactive metabolite of PAF, had no effect in either of the assays. Control and PAF-induced cell proliferation in low-serum medium was inhibited by PAF receptor antagonists present during the extended growth period. The presence of PAF receptor mRNA in human skin fibroblasts was demonstrated by reverse transcriptase-polymerase chain reaction. The presence of a functional receptor was indicated by an early (2 min) transient increase in PKC activity and an increase in fos mRNA after PAF treatment. PAF-induced PKC activity was blocked by pretreatment with either staurosporine (50 nM) or CV3988 (1 microM). These results suggest that PAF is a mitogenic factor that contributes to the known increase in risk of malignancy associated with chronic inflammatory conditions. SN - 0899-1987 UR - https://www.unboundmedicine.com/medline/citation/9433481/Receptor_mediated_and_protein_kinase_dependent_growth_enhancement_of_primary_human_fibroblasts_by_platelet_activating_factor_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0899-1987&date=1997&volume=20&issue=4&spage=366 DB - PRIME DP - Unbound Medicine ER -