Steve Silletti

Tumor cell autocrine motility factor receptor

The ability to locomote and migrate is fundamental to the acquisition of invasive and metastatic properties by tumor cells. Autocrine motility factor (AMF) is a cytokine produced by various tumor cells which stimulates their in vitro motility and in vivo lung-colonizing ability. AMF stimulates cell motility via a receptor-mediated signalling pathway. Signal transduction following binding of AMF to its receptor, a cell surface glycoprotein of 78 kD (gp78), is mediated by a pertussis toxin sensitive G protein, inositol phosphate production and the phosphorylation of gp78. AMF induces gp78 internalization to intracellular tubulovesicles and transport to the leading edge stimulating pseudopodial protrusion and cell motility.

Effect of 12-HETE on the Expression of Autocrine Motility Factor-Receptor and Motility in Melanoma Cells

A 12-lipoxygenase metabolite of archidonic acid, 12-(S)-hydroxyglicosatetraenoic acid (12-(S)- HETE), which is synthesized by cancer cells was tested for its ability to affect the motility of K-1735 murine melanoma cells in culture. Pretreatment of the cells with 12-(S)-HETE at a concentration of 0.1μM stimulated (two-fold) cell migration. An analysis of cell surface for the expression the autocrine motility factor receptor (AMF-R) by immunofluorescence revealed an increase in the amount of AMF-R in the treated cells. These results support the hypothesis that 12(S)-HETE regulate the cell surface expression of various membrane antigens and affects the phenotype of cancer cells.