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Apoptosis and anergy of T cell induced by pancreatic stellate cells-derived galectin-1 in pancreatic cancer



Published on:2016-11-28   Views:182

Abstract

Galectin-1, a β-galactoside-binding proteinimplicated in cancer cell immune privilege, was highly expressed in activatedpancreatic stellate cells (PSCs). This study was designed to investigate therelationship between PSC-derived galectin-1 and tumor immunity in pancreaticcancer. Isolated PSCs were identified as normal pancreas cells (hNPSCs) orpancreatic cancer cells (hCaPSCs) by immunohistochemical staining for α-SMA andvimentin, and galectin-1 expression was evaluated by Western blotting andquantitative RT-PCR. Apoptosis, caspase activity, and cytokine production(IL-6, IL-10, TNF-β, and IFN-γ) of T cells co-cultured with PSCs wereevaluated, and immunohistochemical staining of galectin-1 was correlated withCD3 and clinicopathological variables in 66 pancreatic cancer and 10 normalpancreatic tissue samples. hCaPSCs exhibited higher galectin-1 expression thandid hNPSCs, and hCaPSCs induced higher levels of apoptosis in T cells followingco-culture. hCaPSCs activated caspase-9 and caspase-3 in the mitochondrialapoptotic pathway and stimulated secretion of Th2 cytokines (IL-6 and IL-10)but decreased secretion of Th1 cytokines (TNF-β and IFN-γ), compared withhNPSCs. Immunohistochemical staining indicated that galectin-1 and CD3 weremore highly expressed in pancreatic cancer tissue. Galectin-1 expression washighest in poorly differentiated pancreatic cancer cells and lowest inwell-differentiated pancreatic cancer cells and was associated with tumor size,lymph node metastasis, differentiation, and UICC stage. However, CD3 expressionshowed the opposite trend and was highest in well-differentiated pancreaticcancer cells and was associated with tumor differentiation and UICC stage. Highexpression of galectin-1 was associated with short survival, as was lowexpression of CD3. hCaPSC-derived galectin-1 enhanced apoptosis and anergy of Tcells in pancreatic cancer, which contributes to the immune escape ofpancreatic cancer cells.