ABNORMAL ACCUMULATION OF HYALURONAN MATRIX DIMINISHES CONTACT-INHIBITION OF CELL GROWTH AND PROMOTES CELL MIGRATION

概要

論文の詳細を見る
Elevated hyaluronan biosynthesis and matrix deposition correlates with cell proliferation and migration. We ectopically expressed 3 isoforms of hyaluronan synthase (HAS1, HAS2, or HAS3) in non-transformed rat 3Y1 cells and observed a de novo, massive formation of a hyaluronan matrix that resulted in a paitial 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 transfectans, and occurred with significant alterations in the microfilament organization and N-cadherin distribution at the cell-cell border. Inhibition of a PI3 kinase pathway resulted in reacquisition of the normal epithelial phenotype of HAS2 transfectants, suggesting that the intracellular PI3 kinase signaling regulates diminution of contact inhibition induced by formation of the massive HA matrix. Our observations suggest that hyaluronan and its matrix can modulate contact inhibition of cell growth and migration, and provide the first evidence for functional differences between hyaluronan synthesized by the different HAS proteins.
日本結合組織学会の論文