DR-nm23 expression affects neuroblastoma cell differentiation, integrin expression, and adhesion characteristics

Background and Procedure. Nm23 genefamily has been associated with metastasis sup-pression and differentiation. We studied DR-nm23 during neuroblastoma cells differentia-tion. DR-nm23 expression increased afterretinoic acid induction of differentiation in hu-man cell lines SK-N-SH and LAN-5. Results. Inseveral cell lines, overexpression of DR-nm23was associated with more differentiated pheno-types. SK-N-SH cells increased vimentin ex-pression, increased deposition of collagen typeIV, modulated integrin expression, and under-went growth arrest; the murine neuroblastomacell line N1E-115 showed neurite outgrowthand a striking enhancement of ␤1 integrin ex-pression. Up-regulation of ␤1 integrin was spe-cifically responsible for the increase in the ad-hesion to collagen type I-coated plates. Finally,cells overexpressing DR-nm23 were unable togrowth in soft agar. Conclusions. In conclusion,DR-nm23 expression is directly involved in dif-ferentiation of neuroblastoma cells, and its abil-ity to affects the adhesion to extracellular sub-strates and to inhibit growth in soft agarsuggests an involvement in the metastatic po-tential of neuroblastoma. Med. Pediatr. Oncol.36:93–96, 2001.