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Modulation of neuroblastoma cell differentiation by the extracellular matrix
Author(s) -
Matsushima Hiroshi,
Bogenmann Emil
Publication year - 1992
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910510511
Subject(s) - extracellular matrix , chondroitin sulfate , trypsinization , microbiology and biotechnology , cellular differentiation , cell culture , chemistry , retinoic acid , hyaluronic acid , glycosaminoglycan , biochemistry , matrix (chemical analysis) , biology , trypsin , anatomy , enzyme , genetics , chromatography , gene
The effect of a complex in vitro synthesized extracellular matrix (ECM) and its components on growth and phenotypical differentiation of a human neuroblastoma (NB) cell line (HTLA230) was investigated. Rat smooth‐muscle‐cell (R 22 CIF)‐derived ECM composed of collagen, glycoproteins, and glycosaminoglycans (GAGs) promoted spontaneous neurite outgrowth of HTLA230 cells but did not alter their growth kinetic or cloning efficiency as compared with cells seeded onto gelatin‐coated dishes. The matrix significantly enhanced, quantitatively and qualitatively, the responsiveness of HTLA230 cells to retinoic acid (RA), and a substantially reduced growth rate was observed in the presence of RA with cells grown on the ECM. Biochemical modification of the composition of the R 22 CIF‐matrix by trypsin digestion and/or high‐salt extraction (4 M guanidinium) demonstrated that the ratio of chondroitin sulfate to hyaluronic acid (HA) present in the ECM determines the capacity of the matrix to promote NB differentiation. A human fibroblast (T‐1)‐derived ECM, which has a biochemical composition of the GAG component similar to that of the trypsinized R 22 CIF‐matrix, but which has a high amount of glycoproteins, confirmed these results. Nerve‐growth‐factor (NGF)‐induced differentiation in a variant HTLA 230 cell line was inhibited when cells were grown on an ECM with a low ratio of chondroitin sulfate/HA. The composition of the ECM thus modulates the responsiveness to various differentiation‐inducing agents and alters the phenotype of NB cells. © 1992 Wifey‐Liss, Inc.