title: Cadherin-11 Is a Cell Surface Marker Up-Regulated in Activated Pancreatic Stellate Cells and Is Involved in Pancreatic Cancer Cell Migration.
abstract: 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.
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California; Department of Internal Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Birtolo
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Hung
authors.initials: H
authors.lastname: Pham
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Susan
authors.initials: S
authors.lastname: Morvaridi
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Chintan
authors.initials: C
authors.lastname: Chheda
authors.affiliation: Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California.
authors.forename: Vay Liang W
authors.initials: VL
authors.lastname: Go
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Ptasznik
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Mouad
authors.initials: M
authors.lastname: Edderkaoui
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Weisman
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Erika
authors.initials: E
authors.lastname: Noss
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Brenner
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Brent
authors.initials: B
authors.lastname: Larson
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Maha
authors.initials: M
authors.lastname: Guindi
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address: qiang.wang@cshs.org.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California; Department of Veterans Affairs, VA Greater Los Angeles Health Care System, Los Angeles, California. Electronic address: stephen.pandol@cshs.org.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Pandol
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D058954:Pancreatic Stellate Cells / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; C086960:osteoblast cadherin