ALPHA-V BETA-3 AND ALPHA-V/BETA-5 INTEGRIN DISTRIBUTION IN NEOPLASTICKIDNEY/

Integrins are transmembrane glycoproteins that mediate cell-cell and c ell-matrix interactions. Altered integrin expression may contribute to tumor progression, invasiveness and metastases. The alpha-V/beta-3 (a lpha(v) beta(5); osteopontin/vitronectin receptor) has recently been i mplicated in neovascularization and tumor-induced angiogenesis. alpha( v)-Subunit also associates with beta(5) to form an alpha(v) beta(5)-co mplex, another vitronectin receptor. We studied tissue distribution of alpha(v) beta(3)- and alpha(v) beta(5)-integrins, as well as alpha(1) - and beta(1)-subunits in nephrectomy samples from 7 subjects with loc alized renal cell carcinoma. Grossly and histologically uninvolved reg ions ('normal') from the same nephrectomy specimens were used for comp arison. Integrin expression was studied with specific monoclonal antib odies and the immunoperoxidase technique. alpha(v) beta(3) was express ed in the glomerular epithelial cells, Bowman's capsule, vascular endo thelium, and weakly in tubular epithelial cells. alpha(v) beta(5) had a similar distribution except for minimal expression on vascular endot helium, alpha(1)-Expression was observed in mesangium and but weakly i n Bowman's capsule. beta(1)-Expression was seen in glomerular epitheli al cells, Bowman's capsule, vascular epithelium and tubular epithelial cells. Unlike in 'normals', neoplastic expression was more heterogene ous. alpha(v) beta(3) was expressed in tumor cells in 4/7 cases, vascu lar endothelium in 6/6, and in stroma in 4/7. alpha(v) beta(5) was wea kly expressed in tumor cells in 4/5, vascular endothelium in 5/5, and stroma in 4/5 cases. alpha(1)-Expression was seen in tumor cells in 3/ 7, vascular endothelium in 4/7 and in stroma in 7/7 cases. beta(1)-Exp ression was seen in tumor cells in 7/7 cases, vascular endothelium in 7/7, and in stroma in 4/7 cases. This study delineates the pattern of expression of the alpha(v) beta(3)- and alpha(v) beta(5)-integrins in 'normal' and neoplastic human kidney. Variations in alpha(v) beta(3)- and alpha(v) beta(5)-integrin expression may play a role in normal and neoplastic processes of the kidney.