arousal of cancer-associated stroma overexpression of palladin activates fibroblasts to promote tumor invasion兴奋的癌症相关的基质过度palladin激活成纤维细胞促进肿瘤的侵袭.pdfVIP

Arousal of Cancer-Associated Stroma: Overexpression of Palladin Activates Fibroblasts to Promote Tumor Invasion 1 . 1. 2 2,3 1 1 Teresa A. Brentnall * , Lisa A. Lai , Joshua Coleman , Mary P. Bronner , Sheng Pan , Ru Chen 1 GI Division, Department of Medicine, University of Washington, Seattle, Washington, United States of America, 2 Department of Anatomic Pathology, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America, 3 Division of Anatomic Pathology, University of Utah, Salt Lake City, Utah, United States of America Abstract Background: Cancer-associated fibroblasts, comprised of activated fibroblasts or myofibroblasts, are found in the stroma surrounding solid tumors. These myofibroblasts promote invasion and metastasis of cancer cells. Mechanisms regulating the activation of the fibroblasts and the initiation of invasive tumorigenesis are of great interest. Upregulation of the cytoskeletal protein, palladin, has been detected in the stromal myofibroblasts surrounding many solid cancers and in expression screens for genes involved in invasion. Using a pancreatic cancer model, we investigated the functional consequence of overexpression of exogenous palladin in normal fibroblasts in vitro and its effect on the early stages of tumor invasion. Principal Findings: Palladin expression in stromal fibroblasts occurs very early in tumorigenesis. In vivo, concordant expression of palladin and the myofibroblast marker, alpha smooth muscle actin (a-SMA), occurs early at the dysplastic stages in peri-tumoral stroma and progressively increases in pancreatic tumorigenesis. In vitro introduc