Hyaluronan content in experimental carcinoma is not correlated to interstitial fluid pressure

被引:9
作者
Jacobson, A
Salnikov, A
Lammerts, E
Roswall, P
Sundberg, C
Heldin, P
Rubin, K
Heldin, NE [1 ]
机构
[1] Univ Uppsala Hosp, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden
[2] Biomed Ctr, Dept Med Biochem & Microbiol, SE-75123 Uppsala, Sweden
[3] Biomed Ctr, Ludwig Inst Canc Res, SE-75123 Uppsala, Sweden
关键词
ATC; colon adenocarcinoma; TGF-beta; xenograft tumors;
D O I
10.1016/S0006-291X(03)00872-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-beta1 and -beta3 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. (C) 2003 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:1017 / 1023
页数:7
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