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The cell-surface heterodimers of the integrin family of molecules, which mediate cell-cell and cell-substratum interactions, are likely to be functionally relevant in local and metastatic tumor growth. In the present study we have analyzed whether the alpha 3/beta 1 receptor for collagen, laminin and fibronectin undergoes changes in expression during tumor progression in cutaneous malignant melanoma (CMM). The results of this study have demonstrated that, while low levels of VLA3 expression are detectable in benign lesions, in primary melanomas the heterodimer undergoes progressive increase in expression which correlates with the degree of dermal invasiveness. Metastatic lesions were found VLA3 positive in 82% of cases. Furthermore, the heterodimer is homogeneously expressed in multiple autologous metastases. The presence of VLA3 correlates with detection of at least one of the ligands in 45% of the cases studied. These findings provide additional evidence that tumor progression in CMM is associated with changes in integrin phenotypes which include the alpha 3/beta 1 heterodimer.

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SUMMARY The CCGG and GCGC sites of the human HLA‐DRα gene are hypermethylated in human tissues (including B‐lymphocytes, T‐lymphocytes, muscle, brain, sperm, skin, kidney, suprarenal and mammary glands) and three B‐lymphoid cell lines. Therefore, the HLA‐DRα gene can be transcribed even though extensively methylated. The only exception to the hypermethylated state of the HLA‐DRα gene is represented by one or both of the two HhaI sites (H1 and H2) localized in the 5’portion of the gene. Analysis of the computer‐generated secondary structure of the HLA‐DRα mRNA suggests that the H1 and H2 sites belong to a region (5′‐GAGCGCCCA‐3′/5′‐UGAGCGCUC‐3′) exhibiting extensive base pairing. Therefore, unmethylation of these CG sites can contribute in preventing mCG→TG/CA changes in this region, which would lead to extensive alterations of the secondary structure of the 5’portion of the HLA‐DRα MRNA. On the other hand, the selective pressure to maintain unaltered the methylated CG dinucleotides in the coding regions of the HLA‐DRα gene could be due to codon restrictions, since the majority of the methylation‐related CG→TG or CG→CA variations would generate aminoacid changes. Accordingly, the analysis of different HLA‐DRα genomic sequences indicates that variations of the CpG dinucleotides occur only in the non‐coding portions of the HLA‐DRα gene.