DIFFERENTIAL PATTERNS OF HOX GENE-EXPRESSION ARE ASSOCIATED WITH SPECIFIC INTEGRIN AND ICAM PROFILES IN CLONAL POPULATIONS ISOLATED FROM A SINGLE HUMAN-MELANOMA METASTASIS

Homeobox-containing genes comprise a gene family coding for transcript ion factors involved in normal development. Class I human homeobox (HO X) genes display a peculiar chromosomal organization, perhaps directly related to their function. Aberrant expression of homeobox genes has been associated with both morphological abnormalities and oncogenesis. We have reported that HOX gene expression is (i) specific for normal adult human organs (kidney, colon, lung) and (ii) altered in cancer sp ecimens according to their histological type and stage of tumor progre ssion. Here, we have investigated whether patterns of HOX gene express ion are associated with tumor heterogeneity by analyzing the expressio n of the entire panel of 38 HOX genes in clones isolated from a single human metastatic melanoma cell line (Me 665/2). The differential expr ession of a block of genes located at the 5' end of the HOX C locus al lows melanoma clones to be classified into 2 major groups. The 2 patte rns of HOX gene expression are inversely associated with 2 distinct su rface phenotypes for integrins (VLA-2, VLA-5 and VLA-6) and the adhesi on molecule ICAM-1. The genes of the HOX C locus are silent in the clo nes with high levels of integrins VLA-2, VLA-5 and VLA-6 and of the ad hesion molecule ICAM-1 but actively expressed in the clones with low l evels of ICAM-1 and lacking VLA-2, VLA-5 and VLA-6. Our results indica te that HOX gene expression reflects the intra-tumor heterogeneity of melanoma clones and suggest that the expression of surface molecules i nvolved in cell-cell and cell-matrix interactions may be related to th e patterns of HOX gene expression. (C) 1996 Wiley-Liss, Inc.