Contribution of the extracellular matrix to growth properties of cells from a preneoplastic outgrowth: possible role of hyaluronic acid.
Hyaluronic acid (HA) accumulates around actively growing normal and tumorigenic mammary epithelial cells and has been implicated as a modulator of cell proliferation. We have tested the role of exogenous HA presented in several different forms in in vitro growth regulation of a cell line (CL-S1) derived from preneoplastic mouse mammary tissue. This cell line grows slowly and synthesizes very little HA. We first assessed growth of CL-S1 cells seeded onto actual matrix generated by CL-S1 cells themselves (which has a low HA content) or by a related tumorigenic cell line, +SA, that generates an HA-rich matrix. Growth on both these HA-containing substrata was significantly enhanced above control values on plastic. Growth on the +SA biomatrix was over 5 times greater than on tissue culture plastic and significantly greater than that seen with all other treatments. Differences in growth responses of CL-S1 cells seeded atop CL-S1- and +SA-derived matrices could be attributable to differences in matrix HA content. As a more direct test of this possibility, growth responses of CL-S1 cells to HA covalently bonded to tissue culture dishes and to HA dissolved in culture media were tested. Growth on the prepared HA substrata was consistently twice that on plastic. In soluble form, HA at a concentration of 100 micrograms HA/ml culture medium, stimulated CL-S1 growth 196 and 125% of control in monolayer cultures, respectively, seeded at low (approximately equal to 10(2) viable cells/cm2) and high (approximately equal to 10(4) viable cells/cm2) densities on plastic. Higher HA concentrations inhibited growth at low seeding densities.(ABSTRACT TRUNCATED AT 250 WORDS)
Elstad
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CA
College of Pharmacy, Washington State University, Pullman.
Hosick
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HL
D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003094:Collagen; D003470:Culture Media; D005109:Extracellular Matrix / Q000502:physiology*; D006133:Growth Substances / Q000494:pharmacology; D006820:Hyaluronic Acid / Q000096:biosynthesis / Q000494:pharmacology*; D066298:In Vitro Techniques; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D011230:Precancerous Conditions / Q000473:pathology*
D003470:Culture Media; D006133:Growth Substances; D006820:Hyaluronic Acid; D003094:Collagen