Distribution of extracellular and cytoplasmic domains of the alpha 3 and alpha 6 integrin subunits in solid tumors.

Integrins play an important role in malignant transformation and the invasion of tumors. They mediate cell-cell and cell-matrix interactions and participate in transduction of signals across the plasma membrane, processes dependent on the extracellular and cytoplasmic domains of integrins. We studied a selection of solid tumors by immunohistochemistry using monoclonal antibodies (MAbs) against the extracellular domain and the cytoplasmic variants (A and B) of the alpha 3 and alpha 6 integrin subunits. The tissue-specific expression of ecto- and cyto-domains of alpha 3 and alpha 6 is maintained in a subset of breast, colon, kidney and parotid tumors. In a few breast tumors, there was a switch in variant expression in that alpha 6B was detected instead of alpha 6A in normal breast tissue. In many colon and parotid tumors, one of the variants of alpha 6 was missing, while both were detectable in the corresponding normal tissues. In contrast, coexpression of the alpha 6 variants was found in some kidney tumors, whereas only one of the variants was detected in the normal tissue. In a minority of colon and kidney tumors, the cyto-domains of alpha 3 and alpha 6 were undetectable and total absence of alpha 3 and alpha 6 was noted in a subset of breast, colon, kidney and parotid tumors. These observations show that expression of the integrin variants in tumors varies considerably and support the concept that changes in expression may contribute to malignant behavior.