Hyaluronan content in experimental carcinoma is not correlated to interstitial fluid pressure.
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.
Jacobson
Annica
A
Department of Medical Biochemistry and Microbiology, Biomedical Center, Box 582, SE-751 23 Uppsala, Sweden.
Salnikov
Alexei
A
Lammerts
Ellen
E
Roswall
Pernilla
P
Sundberg
Christian
C
Heldin
Paraskevi
P
Rubin
Kristofer
K
Heldin
Nils-Erik
NE
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
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