GSK3 and PKB/Akt are associated with integrin-mediated regulation of PTHrP, IL-6 and IL-8 expression in FG pancreatic cancer cells

Department of Surgery, University of California, San Diego, CA 92161, USA.
International Journal of Cancer (Impact Factor: 5.01). 04/2005; 114(4):522-30. DOI: 10.1002/ijc.20748
Source: PubMed

ABSTRACT We have demonstrated recently that PTHrP is upregulated in pancreatic adenocarcinoma and that the ECM exerts regulatory control, at least in part, over PTHrP expression. In our present study, we examined the potential signaling interactions between these 2 pathways. Our results demonstrate that, under serum-free conditions, adhesion of FG pancreatic adenocarcinoma cells on Fn is mediated by the alpha5beta1 integrin, whereas adhesion to Type I collagen is mediated by the alpha2beta1 integrin. alpha5beta1 integrin-mediated adhesion to Fn results in a phenotype that includes a reduction in cell proliferation, increased E-cadherin localization in cell-cell contacts, increased beta-catenin localization throughout the cell, inhibition of haptokinetic cell migration, and increased expression of PTHrP, IL-6 and IL-8 relative to alpha2beta1 integrin-mediated adhesion on Type I collagen. A phosphoprotein immunoblotting screen of FG pancreatic cancer cells grown on either Fn or Type I collagen indicates that GSK3 and PKB/Akt are differentially phosphorylated on these 2 substrates. These results implicate GSK3 and PKB/Akt in the integrin-mediated regulation of PTHrP, IL-6 and IL-8 in pancreatic cancer.

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    • "Type I collagen markedly stimulates cytokine expression in metastatic HNSCC cell lines compared with that of the primary cancer cell line. Cytokine expression stimulated by type-I collagen has also been seen in cancer cell lines derived from breast and pancreatic cancers (Grzesiak et al., 2005; Hirtenlehne et al., 2002). Evidence is also presented that cytokines stimulate MMP activity and enhance the invasion of HNSCC cells. "
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