RRC ID 1230
Author Itano N, Atsumi F, Sawai T, Yamada Y, Miyaishi O, Senga T, Hamaguchi M, Kimata K.
Title Abnormal accumulation of hyaluronan matrix diminishes contact inhibition of cell growth and promotes cell migration.
Journal Proc. Natl. Acad. Sci. U.S.A.
Abstract 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 (PI3-kinase) pathway resulted in reacquisition of the normal phenotype of HAS2 transfectants, suggesting that the intracellular PI3-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.
Volume 99(6)
Pages 3609-14
Published 2002-3-19
DOI 10.1073/pnas.052026799
PII 052026799
PMID 11891291
PMC PMC122571
MeSH Agar Animals Cell Count Cell Division Cell Line Cell Movement* Cell Size Cell Transformation, Neoplastic / genetics Contact Inhibition* Cytoskeleton / metabolism Erythrocytes Extracellular Matrix / enzymology Extracellular Matrix / metabolism* Fibroblasts / cytology Fibroblasts / enzymology Fibroblasts / metabolism Flow Cytometry Gene Expression Glucuronosyltransferase / genetics Glucuronosyltransferase / metabolism Glycosyltransferases* Hyaluronan Synthases Hyaluronic Acid / metabolism* Isoenzymes / genetics Isoenzymes / metabolism Membrane Proteins* Microscopy, Electron Phenotype Phosphatidylinositol 3-Kinases / metabolism Rats Sheep Transfection Transferases* Wound Healing Xenopus Proteins*
IF 9.58
Times Cited 204
Human and Animal Cells SV-3Y1-C6 E1A-3Y1-1 3Y1-B clone 1-6