| Research Abstract |
A variety of growth factors stimulate the arachidonate release and prostaglandin production in many types of cells. Both arachidonic acid and prostaglandins are reported to modulate mitogenic activity of these growth factors. Arachidonic acid can affect cellular growth through its conversion to prostaglandins or its ability to stimulate activities of enzymes such as protein kinase C and phospholipase C. In this study, we examined the effects of exogenous arachidonic acid on cellular growth and migration in two types of golden hamster embryo cells(GHE), GHEp38 and GHEp69. When arachidonic acid(10 muM) was added in culture medium of both types of cells, only GHEp69 cells with transformed phenotypes were stimulated to grow. Oleic acid, linoleic acid, and eicosapentaenoic acid also stimulated cell growth, but palmitic acid did not. This stimulation was observed even in the presence of indomethacin. On the other hand, staurosporine, an inhibitor of protein kinase C, abolished the action of
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arachidonic acid to stimulate cell growth. These results suggest that arachidonic acid, but not prostaglandins, stimulates growth of transformed GHE cells through the activation of protein kinase C. When arachidonic acid was examined for the activity to stimulate migration of transformed GHE cells using Boyden chamber, arachidonic acid futher increased EGF-stimulated cell migration.
In contrast, in two cell lines derived from human gastric carcinomas, arachidonic acid was effective in stimulating cell migration, but not in stimulating cell growth. This motility activity of arachidonic acid was observed in the presence of indomethacin, and addition of oleic acid produced no significant effect on migration of human carcinoma cells. These results indicate that the growth and motility responses induced by arachidonic acid differ in different cell types. It will be important to elucidate roles of various fatty acids, prostaglandins, and leukotrienes as a second messenger in signal transduction leading to cell growth and migration. Less
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