title: Pancreatic tumor cells influence the composition of the extracellular matrix.
abstract: The malignant behavior of cancers depends on the microenvironmental context. We investigated compositional alterations of the extracellular matrix (ECM) in pancreatic cancer, with special emphasis on the proteoglycans decorin, lumican, and versican. Compared with normal controls (n=18), marked overexpression of these proteoglycans was observed in pancreatic cancer tissues (n=30) by quantitative RT-PCR (p<0.0001). Immunohistochemistry revealed abundance of proteoglycans in the ECM of pancreatic cancer specimens, whereas tumor cells themselves were devoid of either decorin, lumican or versican. RT-PCR confirmed pancreatic stellate cells (PSCs) as the major source of these proteins. Interestingly, TGFbeta1 and conditioned medium derived from pancreatic cancer cell lines synergistically suppressed the expression of known anti-tumor factors decorin and lumican, but stimulated the expression of pro-metastatic factor versican in cultured PSCs. These findings indicate that malignant cells can actively influence the composition of the ECM through TGFbeta1 and other soluble factors, altering their microenvironment in a tumor-favorable way.
authors.affiliation: Department of General Surgery, University of Heidelberg, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Köninger
authors.forename: Thomas
authors.initials: T
authors.lastname: Giese
authors.forename: Fabio F
authors.initials: FF
authors.lastname: di Mola
authors.forename: Moritz N
authors.initials: MN
authors.lastname: Wente
authors.forename: Irene
authors.initials: I
authors.lastname: Esposito
authors.forename: Max G
authors.initials: MG
authors.lastname: Bachem
authors.forename: Nathalia A
authors.initials: NA
authors.lastname: Giese
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
mesh_terms: D000230:Adenocarcinoma; D000328:Adult; D000368:Aged; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics*; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007632:Keratan Sulfate / Q000235:genetics*; D037181:Lectins, C-Type; D000071234:Lumican; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics*; D011509:Proteoglycans / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D053675:Versicans
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; C000604306:LUM protein, human; D037181:Lectins, C-Type; D000071234:Lumican; D011509:Proteoglycans; C508322:VCAN protein, human; D053675:Versicans; D007632:Keratan Sulfate