Upregulation of mobility in pancreatic cancer cells by secreted S100A11 through activation of surrounding fibroblasts.

Upregulation of mobility in pancreatic cancer cells by secreted S100A11 through activation of surrounding fibroblasts. Oncol Res. 2019 Apr 17;: Authors: Mitsui Y, Tomonobu N, Watanabe M, Kinoshita R, Sumardika W, Youyi C, Murata H, Yamamoto KI, Sadahira T, Rodrigo AGH, Takamatsu H, Araki K, Yamauchi A, Yamamura M, Fujiwara H, Inoue Y, Futami J, Saito K, Iioka H, Kondo E, Nishibori M, Toyooka S, Yamamoto Y, Nasu Y, Sakaguchi M Abstract S100A11, a member of S100 family proteins, is actively secreted from pancreatic ductal adenocarcinoma (PDAC) cells. However, the role of the extracellular S100A11 in PDAC progression remains unclear. In the present study, we investigated the extracellular role of S100A11 in cross-talking between PDAC cells and surrounding fibroblasts in PDAC progression.An abundant S100A11 secreted from pancreatic cancer cells stimulated neighboring fibroblasts through receptor for advanced glycation endproducts (RAGE) upon S100A11 binding, and was followed by not only an enhanced cancer cell motility in vitro but also an increased number of the PDAC-derived circulating tumor cells (CTCs) in vivo. Mechanistic investigation of RAGE downstream in fibroblasts revealed a novel contribution of a mitogen-activated protein kinasekinase kinase (MAPKKK), tumor progression locus 2 (TPL2), which is required for positive regulation of PDAC cell motility through induction of cyclooxygenase 2 (COX2) and itscatalyzed production of pro...
Source: Oncology Research - Category: Cancer & Oncology Tags: Oncol Res Source Type: research