INTEGRINS IN HUMAN-CELLS AND TUMORS

We have studied the distribution of the alpha- and beta-subunits of integrins in developing and adult human kidney as well as in selected other tissues and cultured cells. In cultured cells some of the integrin subunits (beta-1, alpha-1, alpha-2 and alpha-5) colocalize with talin at focal adhesions when plated on an appropriate ligand. Similarly, in tissues the polarization of beta-1-integrins in colocalization with talin appears to indicate adhesive complexes, as demonstrated in adult glomeruli. In human kidney, the alpha subunits of integrins were seen to be segment-specifically expressed already in fetal tissues. In glomeruli the integrin alpha-1 subunit characterized mesangial cells while the alpha-2 and alpha-3 subunits showed immunoreactivity in endothelial cells and podocytes, respectively. In renal tubuli, the alpha-6 subunit, complexed with the beta-1 subunit, showed a typical polarized distribution coaligning with the tubular basement membrane while the alpha-3 and alpha-2 subunits were expressed in distal tubular cells. These results suggested that in kidney the alpha-2-beta-1, alpha-3-beta-1, and alpha-6-beta-1 integrins can function as basement membrane receptors. The alpha-5 subunit was nearly lacking in the kidney and it appears to be mainly expressed in some smooth muscle cells. In other tissues distinct patterns in the expression of integrins were found. Thus, in many glandular epithelial cells the alpha-3-beta-1 integrin appeared to function as a basement membrane receptor while in various stratified epithelia and in the breast such a polarized localization could be found for the alpha-6-beta-4 integrin. Finally, although presenting a clearly polarized distribution for beta-1 integrains, none of the alpha-subunits could be found in cardiac or skeletal muscle cells and none of the integrins could be revealed in neuronal cells of human developing and adult cerebrum or cerebellum, although neurons in peripheral tissues contained abundantly the alpha-6-beta-1 integrin complex. In human tumors, the tumors cells, including also metastastatic tumors, generally presented the same integrins as their tissues of origin. In some poorly differentiated tumors both a population heterogeneity and even a lack of expression or a disorganization of basement membrane receptor integrins was obvious.