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. 2021 Feb;288(3):803-817.
doi: 10.1111/febs.15333. Epub 2020 May 1.

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

Papiya Chakraborty  1 , Shiba Prasad Dash  1 , Nibedita Dalpati  1 , Puneet Kumar  1 , Deepali Jain  2 , Pranita P Sarangi  1
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Free article

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

Papiya Chakraborty et al. FEBS J. 2021 Feb.
Free article

Abstract

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.

Keywords: TAM; cancer; fibulin7-C; immunomodulation; macrophage.

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References

    1. Cassetta L & Kitamura T (2018) Targeting tumor-associated macrophages as a potential strategy to enhance the response to immune checkpoint inhibitors. Front Cell Dev Biol 6, 38.
    1. Xu M, Liu M, Du X, Li S, Li H, Li X, Li Y, Wang Y, Qin Z & Fu Y-X (2015) Intratumoral delivery of IL-21 overcomes anti-Her2/Neu resistance through shifting tumor-associated macrophages from M2 to M1 phenotype. J Immunol 194, 4997-5006.
    1. Poh AR & Ernst M (2018) Targeting macrophages in cancer: from bench to bedside. Front Oncol 8, 49.
    1. DeNardo DG, Brennan DJ, Rexhepaj E, Ruffell B, Shiao SL, Madden SF, Gallagher WM, Wadhwani N, Keil SD & Junaid SA (2011) Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discov 1, 54-67.
    1. Das A, Sinha M, Datta S, Abas M, Chaffee S, Sen CK & Roy S (2015) Monocyte and macrophage plasticity in tissue repair and regeneration. Am J Pathol 185, 2596-2606.

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