Overproduction of hyaluronan by expression of the hyaluronan synthase Has2enhances anchorage-independent growth and tumorigenicity

Citation
R. Kosaki et al., Overproduction of hyaluronan by expression of the hyaluronan synthase Has2enhances anchorage-independent growth and tumorigenicity, CANCER RES, 59(5), 1999, pp. 1141-1145
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER RESEARCH
ISSN journal
0008-5472 → ACNP
Volume
59
Issue
5
Year of publication
1999
Pages
1141 - 1145
Database
ISI
SICI code
0008-5472(19990301)59:5<1141:OOHBEO>2.0.ZU;2-A
Abstract
Hyaluronan (HA) has long been implicated in malignant transformation and tu mor progression. However, due to the lack of molecular tools to directly ma nipulate production of HA, which does not require a core protein for its sy nthesis, our understanding of the role of IU in tumor cells has been largel y circumstantial. In this study, we genetically manipulated the production of HA by transfection of a mammalian Hi synthase Has2 into human HT1080 cel ls and examined the malignant phenotype of transfected cells. We found that increased production of HA promotes anchorage-independent growth and tumor igenicity of the cells. Has2-transfected cells formed greater numbers of co lonies in semisolid medium. Tumors in nude mice derived from Has2-transfect ed cells grew more rapidly and were 2-4 times larger than those derived fro m control cells at termination of experiments. Histological and biochemical analyses of tumors revealed no significant differences in cell density and tissue structures between them, indicating that the larger size of the tum ors was due to enhanced cell proliferation, not to increased accumulation o f tumor stroma or increased angiogenesis. These results demonstrate that HA production by tumor cells per se promotes proliferation of these cells in tissues and provides direct evidence for the role of HA in tumorigenicity.