4.6 Article

Cadherin-11 Is a Cell Surface Marker Up-Regulated in Activated Pancreatic Stellate Cells and Is Involved in Pancreatic Cancer Cell Migration

Journal

AMERICAN JOURNAL OF PATHOLOGY
Volume 187, Issue 1, Pages 146-155

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2016.09.012

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Funding

  1. Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute Developmental Funds for Liver Metastasis Team Grant Research Award Colon, pancreas, and prostate cancer engraftment in the liver metastatic niche
  2. National Center for Advancing Translational Sciences UCLA CTSI grant [UL1TR000124]
  3. Department of Veterans Affairs [I01BX001484, P01CA163200, P50 AA11999, P01DK098108]

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Chronic pancreatitis is a prominent risk factor for the development of pancreatic ductal adenocarcinoma. In both conditions, the activation of myofibroblast-like pancreatic stellate cells (PSCs) plays a predominant role in the formation of desmoplastic reaction through the synthesis of connective tissue and extracellular matrix, inducing local pancreatic fibrosis and an inflammatory response. Yet the signaling events involved in chronic pancreatitis and pancreatic cancer progression and metastasis remain poorly defined. Cadherin-11 (Cad-11, also known as OB cadherin or CDH11) is a cell-to-cell adhesion molecule implicated in many biological functions, including tissue morphogenesis and architecture, extracellular matrix-mediated tissue remodeling, cytoskeletal organization, epithelial-to-mesenchymal transition, and cellular migration. In this study, we show that, in human chronic pancreatitis and pancreatic cancer tissues, Cad-11 expression was significantly increased in PSCs and pancreatic cancer cells. In particular, an increased expression of Cad-11 can be detected on the plasma membrane of activated PSCs isolated from chronic pancreatitis tissues and in pancreatic cancer cells Metastasized to the Liver. Moreover, knockdown of Cad-11 in cancer cells reduced pancreatic Cancer cell migration. Taken together, our data underline the potential role of Cad-11 in PSC activation and pancreatic cancer metastasis.

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