A C-terminal fragment of adhesion protein fibulin-7 inhibits growth of murine breast tumor by regulating macrophage reprogramming.

Papiya Chakraborty, Shiba Prasad Dash, Nibedita Dalpati, Puneet Kumar, Deepali Jain, Pranita P Sarangi

The FEBS journal 2021 Feb

filter terms:

Recent reports have shown that a C-terminal fragment of adhesion protein Fibulin7 (Fbln7-C) could demonstrate both antiangiogenic and anti-inflammatory activities. The current study investigated the potential of Fbln7-C as a modulator of tumor-associated macrophages (TAMs) and its potential as an anticancer therapeutic. Our in vitro data show that Fbln7-C could inhibit the tumor cell line (MDA-MB-231) supernatant-induced reprogramming of human monocytes into immunosuppressive TAMs as indicated by higher expression of pERK1/2 and pSTAT1 molecules, and reduced expression of CD206 protein and arg1, ido, and vegf transcripts in monocytes cultured in the presence of Fbln7-C compared to controls. Interestingly, Fbln7-C-treated macrophages retained their altered phenotype even after the removal of Fbln7-C, and their secretome demonstrated anticancer activities. Finally, in a 4T1-induced murine breast tumor model, intravenous administration of Fbln7-C, following the appearance of measurable tumors, significantly reduced the growth and weight of the tumors. Detailed phenotypic analysis of the infiltrated monocyte/macrophage populations (F480+ Ly6G- CD11b+ ) at day 23 postinduction showed a higher percentage of inflammatory monocytes (F480+ Ly6Chi CD11b+ ) and a delayed differentiation into anti-inflammatory TAMs as evident by their reduced levels of CD206 expression. In conclusion, the above data suggest that Fbln7-C could regulate the tumor environment-induced macrophage reprogramming and has the potential for cancer therapeutics. © 2020 Federation of European Biochemical Societies.

Citation

Papiya Chakraborty, Shiba Prasad Dash, Nibedita Dalpati, Puneet Kumar, Deepali Jain, Pranita P Sarangi. A C-terminal fragment of adhesion protein fibulin-7 inhibits growth of murine breast tumor by regulating macrophage reprogramming. The FEBS journal. 2021 Feb;288(3):803-817