title: Hyaluronan content in experimental carcinoma is not correlated to interstitial fluid pressure.
abstract: Mechanism(s) for generation of the high tumor interstitial fluid pressure (TIFP) that is characteristic of carcinoma is not known. We investigated the role of hyaluronan, the major water-binding polysaccharide of the extracellular matrix, for the generation of a high TIFP. A human anaplastic thyroid carcinoma (KAT-4) xenografted to athymic mice and a syngeneic rat colon carcinoma (PROb) were used. Neither KAT-4 nor PROb cells produced hyaluronan (HA) in culture, however, both cell lines produced factors that stimulated HA-synthesis by cultured fibroblasts. Modulating hyaluronan levels by transfection of PROb carcinoma cells with hyaluronan synthase-2 revealed no correlation between hyaluronan content and TIFP. Furthermore, lowering of TIFP by treating KAT-4 tumors with a specific inhibitor of TGF-beta 1 and -beta 3 did not change the concentration of hyaluronan in the tumors. In summary, our results suggest that a modulation of hyaluronan content is not a major pathogenetic mechanism for the generation of the characteristically high TIFP in malignant carcinomas.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Biomedical Center, Box 582, SE-751 23 Uppsala, Sweden.
authors.forename: Annica
authors.initials: A
authors.lastname: Jacobson
authors.forename: Alexei
authors.initials: A
authors.lastname: Salnikov
authors.forename: Ellen
authors.initials: E
authors.lastname: Lammerts
authors.forename: Pernilla
authors.initials: P
authors.lastname: Roswall
authors.forename: Christian
authors.initials: C
authors.lastname: Sundberg
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Heldin
authors.forename: Kristofer
authors.initials: K
authors.lastname: Rubin
authors.forename: Nils-Erik
authors.initials: NE
authors.lastname: Heldin
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000378:metabolism; D005110:Extracellular Space; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000032:analysis* / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D011312:Pressure; D051381:Rats; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; C508962:Tgfb1 protein, rat; C509045:Tgfb3 protein, mouse; C509046:Tgfb3 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3; D006820:Hyaluronic Acid