NEUROTROPHIN-TRK RECEPTOR INTERACTIONS IN NEOPLASIA - A POSSIBLE ROLEIN INTERSTITIAL AND PERINEURAL INVASION IN DUCTAL PANCREATIC-CANCER

Autocrine and paracrine influences of growth factors play a critical r ole in the regulation of the growth, survival, differentiation, and in vasion potential of tumor cells. These influences on the neoplastic ph enotype are particularly important in those cancers in which tumor-str oma interactions constitute important components of tumor development, as exemplified by prostatic, breast, and pancreatic carcinomas. The n eurotrophins and their corresponding Trk and p75(NGFR) receptor subtyp es are families of growth factors and receptors that have received rel atively little attention with respect to neoplasia. This review attemp ts to summarize their biochemical properties, their role in neuronal a nd non-neuronal systems, and their involvement in the development of a variety of cancers, particularly those in which perineural invasion a nd/or metastasis to the CNS are a part of the pathophysiological prese ntation. In this regard, we have focused on our studies of neurotrophi n-Trk/p75(NGFR) expression and interactions in pancreatic ductal carci noma (PDAC) and their potential role in the perineural invasive phenot ype characteristic of this cancer.