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[Cancer Research 59, 2499-2504, May 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 2499-2504, May 15, 1999]
© 1999 American Association for Cancer Research

Tumor Biology

Relationship between Hyaluronan Production and Metastatic Potential of Mouse Mammary Carcinoma Cells1

Naoki Itano2, Takahiro Sawai, Osamu Miyaishi and Koji Kimata2

Institute for Molecular Science of Medicine, Aichi Medical University, Nagakute, Aichi 480-1195 [N. I., T. S., K. K.], and Department of Basic Gerontology, National Institute for Longevity Sciences, Obu, Aichi 474-8522 [O. M.], Japan

To investigate the roles of hyaluronan produced by cancer cells in cancer metastasis, the metastatic potential of the highly metastatic mouse mammary carcinoma FM3A HA1 cell line was compared with those of hyaluronan-deficient mutant cells. Five different mutant clones showed markedly reduced hyaluronan production and lacked the ability to form hyaluronan-rich pericellular coats. These mutant clones displayed significant decreases in metastatic ability compared with the parental cells after i.v. injection into syngeneic mice. These results suggested that the decreased hyaluronan production caused not only the lack of matrix formation but also decreased metastatic potential of the cancer cells. Expression of mouse hyaluronan synthase 1 (HAS1) by transfection into HAS- cells defective in hyaluronan synthase activity rescued hyaluronan matrix formation as well as hyaluronan production. Lung metastasis after i.v. injection of HAS1 transfectants was also recovered significantly. The results provide direct evidence for the involvement of hyaluronan in cancer metastasis.




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