Retinoic acid alters the mechanism of attachment of malignant astrocytoma and neuroblastoma cells to thrombospondin-1

Citation
V. Pijuan-thompson et al., Retinoic acid alters the mechanism of attachment of malignant astrocytoma and neuroblastoma cells to thrombospondin-1, EXP CELL RE, 249(1), 1999, pp. 86-101
Citations number
56
Categorie Soggetti
Cell & Developmental Biology
Journal title
EXPERIMENTAL CELL RESEARCH
ISSN journal
00144827 → ACNP
Volume
249
Issue
1
Year of publication
1999
Pages
86 - 101
Database
ISI
SICI code
0014-4827(19990525)249:1<86:RAATMO>2.0.ZU;2-8
Abstract
Based on the hypothesis that the attachment of neuroectodermal cells to thr ombospondin-1 (TSP-1) may affect tumor spread and play a role in the anti-t umor effects of retinoic acid, we investigated the expression of TSP-1 in t hese cells in situ and the effect of retinoic acid on the morphology of TSP -1-adherent neuroblastoma (SK-N-SH) and malignant astrocytoma (U-251MG) cel ls in vitro. TSP-1-adherent SK-N-SH cells demonstrated process outgrowth, w ith further neuronal differentiation after retinoic acid treatment, consist ent with the in situ studies showing that TSP-1 expression occurs in a diff erentiation-specific manner in neuroblastic tumors, TSP-1-adherent U-251MG; cells failed to spread; however, after retinoic acid treatment the cells d emonstrated broad lamellipodia containing radial actin fibers and organizat ion of integrins alpha 3 beta 1 and alpha 5 beta 1 in clusters in lamellipo dia and filopodia, The attachment of both SK-N-SH and U-251MG cells to TSP- 1 was found to be mediated by heparan sulfate proteoglycans, integrins, and the CLESH-1 adhesion domain first identified in CD36, Heparin and hepariti nase treatment inhibited TSP-1 attachment. Integrins alpha 3 beta 1 and alp ha 5 beta 1 mediated TSP-1 attachment of SK-N-SH cells, and integrins alpha 3 beta 1, alpha 5 beta 1, and alpha v beta 3 mediated TSP-1 attachment of U-251MG: cells. Attachment was dependent on the RGD sequence which is locat ed in the carboxy-terminus of TSP-1, Treatment with a pharmacologic dosage of retinoic acid altered the TSP-1 cell adhesion mechanism in both cell lin es in that neither heparin nor micromolar concentrations of the RGD peptide inhibited attachment; after treatment, attachment was inhibited by the CSV TCG peptide located in the type I repeat domain of TSP-1 and a recombinant adhesion domain (CLESH-1) from CD36. Expression of CD36 was found in the re tinoic acid-treated U-251MG; cells. These data indicate that neuroectoderma lly derived cells utilize several mechanisms to attach to TSP-1, and these are differentially modulated by treatment with retinoic acid. These data al so suggest that the CSVTCG sequence of TSP-1 modulates or directs cytoskele tal organization in neuroblastoma and astrocytoma cells. (C) 1999 Academic Press.