Mast Cell Targeted Chimeric Toxin Can Be Developed as an Adjunctive Therapy in Colon Cancer Treatment.

Ailin Tao,Renren Shi,Zhuofang Hao,Shan Wang,Zehong Zou,Junyan Zhang,Linmei Li,Xueting Liu

doi:10.3390/toxins8030071

Abstract

The association of colitis with colorectal cancer has become increasingly clear with mast cells being identified as important inflammatory cells in the process. In view of the relationship between mast cells and cancer, we studied the effect and mechanisms of mast cells in the development of colon cancer. Functional and mechanistic insights were gained from ex vivo and in vivo studies of cell interactions between mast cells and CT26 cells. Further evidence was reversely obtained in studies of mast cell targeted Fcε-PE40 chimeric toxin. Experiments revealed mast cells could induce colon tumor cell proliferation and invasion. Cancer progression was found to be related to the density of mast cells in colonic submucosa. The activation of MAPK, Rho-GTPase, and STAT pathways in colon cancer cells was triggered by mast cells during cell-to-cell interaction. Lastly, using an Fcε-PE40 chimeric toxin we constructed, we confirmed the promoting effect of mast cells in development of colon cancer. Mast cells are a promoting factor of colon cancer and thus also a potential therapeutic target. The Fcε-PE40 chimeric toxin targeting mast cells could effectively prevent colon cancer in vitro and in vivo. Consequently, these data may demonstrate a novel immunotherapeutic approach for the treatment of tumors.

Highlights

IntroductionTumor development depends on the balance of tumor promoting and anti-tumor effects in vivo
Tumor development depends on the balance of tumor promoting and anti-tumor effects in vivo.Cancer regulation comes from the tumor cell itself and the surrounding microenvironment
We evaluated the expression of vascular endothelial growth factor (VEGF) and TGF-β, which significantly

Summary

Introduction

Tumor development depends on the balance of tumor promoting and anti-tumor effects in vivo. Cancer regulation comes from the tumor cell itself and the surrounding microenvironment. Immune cells are an important component of the tumor microenvironment. The most common immune cells in the tumor microenvironment are T cells and tumor-associated macrophages (ATMs). T cells in the tumor microenvironment include cytotoxic T cells and helper T cells that can have either a tumor suppressing or tumor promoting role [1]. ATMs are the most numerous of the inflammatory cells in tumor stroma and can secrete a variety of proinflammatory cytokines, growth factors and chemokines

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