Pancreatic tumor cells influence the composition of the extracellular matrix

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 ov...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2004-09, Vol.322 (3), p.943-949
Main Authors: Köninger, Jörg, Giese, Thomas, di Mola, Fabio F., Wente, Moritz N., Esposito, Irene, Bachem, Max G., Giese, Nathalia A., Büchler, Markus W., Friess, Helmut
Format: Article
Language:English
Subjects:
Adenocarcinoma
Adult
Aged
Chondroitin Sulfate Proteoglycans - genetics
Decorin
Extracellular matrix
Extracellular Matrix Proteins - genetics
Female
Gene Expression Regulation, Neoplastic - genetics
Humans
Immunohistochemistry
Keratan Sulfate - genetics
Lectins, C-Type
Lumican
Male
Middle Aged
Pancreatic cancer
Pancreatic Neoplasms - genetics
Pancreatic stellate cells
Proteoglycans - genetics
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Versican
Versicans
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Summary: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, TGFβ1 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 TGFβ1 and other soluble factors, altering their microenvironment in a tumor-favorable way.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2004.08.008