Blocking of CDCP1 cleavage inhibits triple negative breast cancer metastasis

Abstract

The most aggressive breast cancer subtype Triple Negative Breast Cancer (TNBC) is characterized by a high mortality rate related to metastasis development, and it still lacks efficient therapeutic strategy able to block its progression. Recently, the cell-surface glycoprotein CDCP1 has been identified as a marker of TNBC aggressiveness. CDCP1 is overexpressed in a vast number of malignancies and is a key driver of their progression and metastasis. It is emerging that the CDCP1 cleavage promotes different steps of the metastatic cascade: anoikis resistance, migration, and survival of cancer cells conferring them intravasation, extravasation, and dissemination potential. In TNBC, CDCP1 has been found mostly present in the cleaved form (cCDCP1) and involved in the promotion of cell migration. Based on this evidence, our study aims to elucidate the role of cCDCP1 in the different steps of the TNBC metastatic cascade and to determine if the blocking of CDCP1 cleavage could represent a new therapeutic approach to block TNBC metastasis. For this purpose, we investigated the effect of blocking the cleavage of CDCP1 through the monoclonal antibody 41-2, on proliferation, survival, migration, and invasion potential of the MDA-MB-231 cell line, TNBC cells known to overexpress CDCP1. We then exploited the chick embryo ChorioAllantoic Membrane (CAM) metastasis model to study how CDCP1 cleavage blockage could affect in vivo metastatic process. Interestingly, our preliminary results obtained using preclinical models indicate that cCDCP1 sustains TNBC cell survival and metastasis. Thus, targeting CDCP1 cleavage could represent an effective therapeutical approach to inhibit TNBC tumor cells dissemination.