Cell Transformation, Invasion, and Angiogenesis: A Regulatory Role for Ornithine Decarboxylase and Polyamines?

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Abstract
In this issue of the Journal, Kubota et al. (1) report that overexpression of ornithine decarboxylase (ODC) triggers mitogen-activated protein (MAP) kinase activity, which in turn implies a proportional increase in invasiveness. They demonstrate that transfection of mouse 10T12 fibroblasts with rat ODC complementary DNA (cDNA) elicited morphologic transformation; the ODC transformants formed colonies in monolayer tissue culture and proliferated in semisolid soft agar. Kubota et al. suggest that the ODC-induced cell transformation mechanism can be explained, at least in part, by activation of the MAP kinase pathway, since the ODC transformants that they studied displayed increased protein kinase activity against myelin basic protein used as an MAP kinase substrate in in-gel assays. In addition, they postulate that deregulated ODC activity may influence invasion of a cancer cell. This was evidenced by migration of ODC transformants through a reconstituted basement membrane-coated filter in Boyden chambers in vitro. Furthermore, Kubota et al. show increased secretion of matrix metalloproteinase (MMP)-2, a 72-kd progelatinase considered to be one of the key players in extracellular matrix degradation. The results obtained by these investigators provide strong evidence that ODC activity and polyamines may affect a number of processes that have an impact on tumor development, including abnormal cell proliferation and invasion.