Low expression of β1, α2 and α3 subunits of VLA integrins in malignant mammary tumours

Abstract

The Very Late Antigens (VLAs) are αβ heterodimeric transmembrane proteins mediating cell–substratum as well as cell–cell interactions. Changes in their expression and/or function seem to occur in a number of invasive carcinomas and may at least in part explain their abnormal patterns of growth and differentiation. Using monoclonal antibodies to the β₁ (DH12, A1A-5), α₂ (B1.515) and α₃ (E1.56) chains, VLA-2 (α₂β₁) and VLA-3 (α₃β₁) were studied on cryostat sections of three fibroadenomas and 43 invasive breast carcinomas (29 ductal, 14 lobular) by the avidin–biotin complex immunoperioxidase technique. In non-neoplastic breast tissue and in fibroadenomas VLA-2 and VLA-3 were expressed by myoepithelial cells and on the basolateral surface of the luminal cells. There was weak or absent expression of α₂, α₃ and the common β₁ chain in the majority of invasive carcinomas compared to the adjacent normal breast epithelium and preinvasive (in-situ) carcinomas. In addition, the expression of the α₂ chain of VLA-2 was reduced significantly (P < 0.005) in the poorly differentiated ductal breast carcinomas (Grade III) compared to the well (Grade I) and moderately (Grade II) differentiated ductal tumours. These data give further evidence that loss or down-regulation of VLA-2 and VLA-3 occur relatively frequently in invasive cancers, and, at least in the invasive ductal breast carcinomas. Loss of an extracellular matrix receptor controlling growth and differentiation seems to be one of the abnormalities underlying the progression towards an undifferentiated morphology.