Platelet-activating factor activates mitogen-activated protein kinases, inhibits proliferation, induces differentiation and suppresses the malignant phenotype of human colon carcinoma cells.
Recent studies suggest that the action of platelet-activating factor (PAF), a potent phospholipid modulator of allergic and inflammatory reactions, is diverse and functions as a modulator of a variety of physiological and pathological events in many cell types and tissues. Its role (if any) in modulating the proliferation, transformation and/or differentiation of epithelial colonic cells, however, is not known. In this study, we showed that PAF is biologically active in epithelial-derived human colon carcinoma cells with different phenotypic properties. These cells expressed the PAF receptor. PAF activated three prominent mitogen-activated protein kinase modules (ERK, p38MAPK and Jun N-terminal kinases) in these cells, inhibited proliferation and induced differentiation (measured by the induction of Waf1/p21 and the induction of the differentiation-related marker CEA). The net effect of PAF treatment was the suppression of malignant cell behavior (measured by anchorage-independent growth and cellular invasion). It is concluded that PAF is a modulator of proliferation and differentiation in human epithelial-derived colon carcinoma cells.
Wang
Hongmei
H
Division of Pathology and Laboratory Medicine, Department of Molecular Pathology, The Unversity of Texas, MD Anderson Cancer Center, Houston 77030, USA.
Chakrabarty
Subhas
S
D002277:Carcinoma / Q000473:pathology*; D002454:Cell Differentiation; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000473:pathology*; D006801:Humans; D048748:MAP Kinase Kinase Kinase 3; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010960:Plasminogen Activators / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases
D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048748:MAP Kinase Kinase Kinase 3; D020930:MAP Kinase Kinase Kinases; C482625:MAP3K3 protein, human; D010960:Plasminogen Activators