Work

Anticancer effect of a single-chain variable fragment against pro-matrix metalloproteinase-7 in colon cancer

Year: 2024

Type: article

Abstract: • A single-chain variable fragment (1B7)-Fc fusion antibody effectively disrupts the interaction between MMP-7 and SDC-2. • 1B7-Fc fusion antibody exhibits significant anticancer effects against colon cancer cells and in mouse models. • 1B7-Fc has a promising therapeutic potential in the field of treatment for colon cancer. Disrupting the interaction between matrix metalloproteinase-7 (MMP-7) and syndecan-2 (SDC-2) can yield anticancer effects in colon cancer cells. Here, a single-chain variable fragment (scFv) targeting the pro-domain of MMP-7 was generated as a potential candidate anticancer agent. Among the generated scFvs, those designated 1B7 and 1C3 showed the strongest abilities to inhibit the ability of MMP-7 pro-domain to directly interact with SDC-2 in vitro and decrease the cancer activities of human HT29 colon adenocarcinoma cells. Consistently, 1B7 and 1C3 inhibited the cell-surface localization of pro-MMP-7, reduced the gelatinolytic activity of MMP-7, and suppressed the cancer activities of metastatic HCT116 human colon carcinoma cells. Notably, 1B7 inhibited the primary tumor growth and lung metastasis of CT26 mouse colon cancer cells in a mouse model. Compared to 1B7, the 1B7-Fc fusion antibody showed better anti-tumorigenic activity against HCT116 cells in culture and a syngeneic mouse model. Together, these data suggest that 1B7-Fc exerts anticancer effects by interfering with the interaction of MMP-7 and SDC-2 and could be a promising therapeutic antibody for colon cancer.

Source: Matrix Biology

DOI: 10.1016/j.matbio.2024.12.009