イタノ ナオキ   ITANO NAOKI
  板野 直樹
   所属   京都産業大学  生命科学部 先端生命科学科
   職種   教授
言語種別 英語
発行・発表の年月 2002/03
形態種別 研究論文
査読 査読あり
標題 Abnormal accumulation of hyaluronan matrix diminishes contact inhibition of cell growth and promotes cell migration
執筆形態 その他
掲載誌名 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
出版社・発行元 NATL ACAD SCIENCES
巻・号・頁 99(6),pp.3609-3614
著者・共著者 N Itano,F Atsumi,T Sawai,Y Yamada,O Miyaishi,T Senga,M Hamaguchi,K Kimata
概要 Elevated hyaluronan biosynthesis and matrix deposition correlates with cell proliferation and migration. We ectopically expressed three isoforms of hyaluronan synthase (HAS1, HAS2, or HAS3) in nontransformed rat 3Y1 cells and observed a de novo, massive formation of a hyaluronan matrix that resulted in a partial loss of contact-mediated inhibition of cell growth and migration. All three HAS transfectants showed an enhanced motility in scratch wound assays, and a significant increase in their confluent cell densities. In high-density cultures, the HAS transfectants had a fibroblastic cell shape and markedly formed overlapping cell layers. This phenotype was more pronounced in the HAS2 transfectants than HAS1 or HAS3 transfectants, and occurred with significant alterations in the microfilament organization and N-cadherin distribution at the cell-cell border. Inhibition of a phosphatidylinositol 3-kinase (P13-kinase) pathway resulted in reacquisition of the normal phenotype of HAS2 transfectants, suggesting that the intracellular P13-kinase signaling regulates diminution of contact inhibition induced by formation of the massive hyaluronan matrix. Our observations suggest that hyaluronan and its matrix can modulate contact inhibition of cell growth and migration, and provide evidence for functional differences between hyaluronan synthesized by the different HAS proteins.
DOI 10.1073/pnas.052026799
ISSN 0027-8424