Integrins in human cells and tumors

Abstract

We have studied the distribution of the α- and β-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 (β₁, α₁, α₂ and α₅) colocalize with talin at focal adhesions when plated on an appropriate ligand. Similarly, in tissues the polarization of β₁-integrins in colocalization with talin appears to indicate adhesive complexes, as demonstrated in adult glomeruli. In human kidney, the α subunits of integrins were seen to be segment-specifically expressed already in fetal tissues. In glomeruli the integrin α₁ subunit characterized mesangial cells while the α₂ and α₃ subunits showed immunoreactivity in endothelial cells and podocytes, respectively. In renal tubuli, the α₆ subunit, complexed with the β₁ subunit, showed a typical polarized distribution coaligning with the tubular basement membrane while the α₃ and α₂ subunits were expressed in distal tubular cells. These results suggested that in kidney the α₂β₁, α₃β₁, and α₆β₁ integrins can function as basement membrane receptors. The α₅ 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 α₃β₁ 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 α₆β₄ integrin. Finally, although presenting a clearly polarized distribution for β₁ integrins, none of the α 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 α₆β₁ integrin complex. In human tumors, the tumor 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.