Cell substrate adhesion is a prerequisite for invasion and the subsequent formation of
metastases. Therefore, we designed
monoclonal antibodies (MAbs) against
epitopes on the extracellular cell membrane domain of SK-BR-3 cells. One of the
antibodies, called
MAb 14C5, binds to an extracellular
epitope of a plasma membrane
antigen of SK-BR-3 and MCF-7 human
breast cancer cells. This
MAb 14C5 is able to inhibit cell substrate adhesion, not only on culture-treated
plastic but also on host tissue, and therefore prevents invasion and
metastases. We evaluated the tissue distribution of the 14C5
antigen by immunohistochemistry. The
antigen is specifically overexpressed in 64% of invasive ductal
adenocarcinomas of the breast (n = 33), in all investigated cases of invasive
squamous cell carcinoma (n = 7) and in 40% of basocellular
carcinomas of the skin (n = 5). The 14C5 molecule is located on the cell membrane of the
carcinoma cells. However, when the
tumor is characterized by a highly invasive phenotype, 65% of the cases also show an extensive stromal expression on the fibroblasts between the
tumor cells (n = 71). This stromal expression is caused by the presence of the 14C5
antigen on the membrane of the adjacent fibroblasts. In normal tissues as well as in the stroma surrounding in situ
carcinomas of the breast (n = 15), no expression of the 14C5
antigen occurred. A 90-kDa
protein was purified from lysates of human
breast cancer cells using a 14C5 MAb
Sepharose column and is considered as the
antigen recognized by the
MAb 14C5.