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Miknyoczki SJ , Lang D , Huang LY , Klein-Szanto AJP , Dionne CA , Ruggeri BA
Neurotrophins and Trk receptors in human pancreatic ductal adenocarcinoma: Expression patterns and effects on in vitro invasive behavior
International Journal of Cancer. 1999 May 5;81(3) :417-427
AbstractThe aggressive and highly metastatic behavior observed in pancreatic ductal adenocarcinoma (PDAC) may be due to autocrine and/or paracrine interactions (tumor/stromal) involving altered expression of peptide growth factors and their corresponding receptors, The neurotrophin (NT) growth factor family and their cognate receptors have been demonstrated to play a role in the invasiveness, chemotactic behavior and tumor cell survival of both neuronal and non-neuronal cancers, We hypothesized that aberrant expression of the NTs and/or the Trk receptors may contribute to the malignant phenotype of PDAC, specifically tumor cell invasiveness, through autocrine and/or paracrine interactions. In this study, we examined the expression of NTs, Trks and p75(NGFR) by immunohistochemical and in situ hybridization analyses in both normal (n = 14) and neoplastic pancreas (n = 47) and PDAC-derived cell lines (n = 6), Further, we evaluated the effects of various NTs on the in vitro invasive and chemotactic behavior on 6 human PDAC-derived cell lines in a modified Boyden chamber assay, Brain-derived nerve growth factor (BDNF), NT-3, NT-4/5 and Trks A, B and C exhibited diffuse cytoplasmic and membranous immunostaining patterns in both the ducts and the acini of the exocrine pancreas and the islets of the endocrine pancreas of both normal and PDAC specimens, NT expression was primarily within the stromal compartment of the tumor, while Trk expression was weak or absent. We observed a 68%, 64% and 66% increase in the expression of Trks A, B and C, respectively, in the ductal elements of the PDAC samples examined compared with the normal adjacent tissue. Invasiveness of 4 of 6 PDAC cell lines was significantly inhibited (p < 0.05) when the cells were incubated with inn ng/ml NT, However, when select cell lines were incubated with lower concentrations of NT-3 and BDNF (0, 1, 5, 25 and 50 ng/ml), invasiveness was significantly stimulated (p < 0.05) through the Matrigel matrix. Collectively, our data suggest the possibility that paracrine and/or autocrine NT-Trk interactions may influence the phenotype (possibly the invasive behavior) of PDAC. (C) 1999 Wiley-Liss, Inc.
NotesTimes Cited: 15 English Article 182DH INT J CANCER