Neurotrophin-Trk receptor interactions in neoplasia: a possible role in interstitial and perineural invasion in ductal pancreatic cancer

Autocrine and paracrine influences of growth factors play a critical role in the regulation of the growth, survival, differentiation, and invasion potential of tumor cells. These influences on the neoplastic phenotype are particularly important in those cancers in which tumor-stroma interactions constitute important components of tumor development, as exemplified by prostatic, breast, and pancreatic carcinomas. The neurotrophins and their corresponding Trk and p75(NGFR) receptor subtypes are families of growth factors and receptors that have received relatively little attention with respect to neoplasia. This review attempts to summarize their biochemical properties, their role in neuronal and non-neuronal systems, and their involvement in the development of a variety of cancers, particularly those in which perineural invasion and/or metastasis to the CNS are a part of the pathophysiological presentation. In this regard, we have focused on our studies of neurotrophin-Trk/p75(NGFR) expression and interactions in pancreatic ductal carcinoma (PDAC) and their potential role in the perineural invasive phenotype characteristic of this cancer.