Published in Cancer Detection and Prevention 1995; 19(1).

Retinoic acid differentially modulates integrin expression on two neuroblastoma cell lines

R Falcioni, C Gaetano, C D'Angelo¹, A Melchiorri², A Albini² and A Sacchi

The expression of integrins can be regulated by growth and differentiation factors and the expression of different integrins may be up- or down-regulated depending on the differentiation state of a given cell. In the present work we investigated the modulation of integrin expression induced by treatment with 5muM all-trans retinoic acid (RA) on the neuroblastoma cell lines LA- N-5 and SK-N-AS. These cell lines are respectively high (LA-N-5) and low (SK-N-AS) sensitive to retinoic acid treatment in terms of growth inhibition and neuronal like-differentiation. Fluorescence- activated cell sorting (FACS) analysis and immunoprecipitation revealed that the integrin Beta4 is up- regulated in presence of RA in the SK-N-AS cell line. In addition while the levels of Alfa6 integrin subunit and AlfavBeta5 vitronectin receptor appear unaffected by RA we found a marked up-regulation of AlfavBeta3 vitronectin receptor. Conversely the RA treatment LA-N-5 cell line doesn't modulate almost all the integrins we examined but affec dramatically the vitronectin receptor (VNR). In fact, this cell line express both VNR AlfavBeta3 and AlfavBeta5 but after RA treatment AlfavBeta5 is dramatically up-regulated. Based on our observations we propose that the two neuroblastoma cell lines LA-N-5 and SK-N- AS treated with RA may be induced to differentiate along two different pathways. Experiments are in progress to define whether RA treatment induces distinct differentiation pathways on the two neuroblastoma cell lines and may also influence invasive capacity. Partially supported by Associazione Italiana per la Ricerca sul Cancro (A.I.R.C.).

Paper presented at the International Symposium on the Impact of Biotechnology on Predictive Oncology and Therapy; Boston, Massachusetts; December 11 - 13, 1994; in the section on Diagnostic Techniques.

http://www.cancerprev.org/Journal/Issues/19/1/309/1212