Relationship between hyaluronan production and metastatic potential of mouse mammary carcinoma cells.
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.
Itano
N
N
Institute for Molecular Science of Medicine, Aichi Medical University, Nagakute, Japan.
Sawai
T
T
Miyaishi
O
O
Kimata
K
K
D000818:Animals; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D002999:Clone Cells / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016695:Glycosyltransferases; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D008565:Membrane Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000502:physiology; D009368:Neoplasm Transplantation; D011993:Recombinant Fusion Proteins / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014166:Transferases; D014407:Tumor Cells, Cultured; D029867:Xenopus Proteins
D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D029867:Xenopus Proteins; D006820:Hyaluronic Acid; D014166:Transferases; D016695:Glycosyltransferases; D014453:Glucuronosyltransferase; C056944:HAS1 protein, Xenopus; D000076002:Hyaluronan Synthases