title: Mast Cell Targeted Chimeric Toxin Can Be Developed as an Adjunctive Therapy in Colon Cancer Treatment.
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.
authors.affiliation: The Second Affiliated Hospital of Guangzhou Medical University, Guangdong Provincial Key Laboratory of Allergy &amp; Clinical Immunology, The State Key Clinical Specialty in Allergy, The State Key Laboratory of Respiratory Disease; Guangzhou 510260, China. april0860@sina.cn.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: The Second Affiliated Hospital of Guangzhou Medical University, Guangdong Provincial Key Laboratory of Allergy &amp; Clinical Immunology, The State Key Clinical Specialty in Allergy, The State Key Laboratory of Respiratory Disease; Guangzhou 510260, China. lilinmei_sysu@163.com.
authors.forename: Linmei
authors.initials: L
authors.lastname: Li
authors.affiliation: The Second Affiliated Hospital of Guangzhou Medical University, Guangdong Provincial Key Laboratory of Allergy &amp; Clinical Immunology, The State Key Clinical Specialty in Allergy, The State Key Laboratory of Respiratory Disease; Guangzhou 510260, China. renrenshi1988@163.com.
authors.forename: Renren
authors.initials: R
authors.lastname: Shi
authors.affiliation: The Second Affiliated Hospital of Guangzhou Medical University, Guangdong Provincial Key Laboratory of Allergy &amp; Clinical Immunology, The State Key Clinical Specialty in Allergy, The State Key Laboratory of Respiratory Disease; Guangzhou 510260, China. xiaoyeliu1984@sina.com.
authors.forename: Xueting
authors.initials: X
authors.lastname: Liu
authors.affiliation: The Second Affiliated Hospital of Guangzhou Medical University, Guangdong Provincial Key Laboratory of Allergy &amp; Clinical Immunology, The State Key Clinical Specialty in Allergy, The State Key Laboratory of Respiratory Disease; Guangzhou 510260, China. allergy_zhang@sina.cn.
authors.forename: Junyan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The Second Affiliated Hospital of Guangzhou Medical University, Guangdong Provincial Key Laboratory of Allergy &amp; Clinical Immunology, The State Key Clinical Specialty in Allergy, The State Key Laboratory of Respiratory Disease; Guangzhou 510260, China. zouzehong123@126.com.
authors.forename: Zehong
authors.initials: Z
authors.lastname: Zou
authors.affiliation: The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China. zhuofanghao@sina.com.
authors.forename: Zhuofang
authors.initials: Z
authors.lastname: Hao
authors.affiliation: The Second Affiliated Hospital of Guangzhou Medical University, Guangdong Provincial Key Laboratory of Allergy &amp; Clinical Immunology, The State Key Clinical Specialty in Allergy, The State Key Laboratory of Respiratory Disease; Guangzhou 510260, China. taoailin@gzmu.edu.cn.
authors.forename: Ailin
authors.initials: A
authors.lastname: Tao
mesh_terms: D036002:ADP Ribose Transferases / Q000276:immunology*; D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000276:immunology* / Q000378:metabolism; D005098:Exotoxins / Q000276:immunology*; D000922:Immunotoxins / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017455:Receptors, IgE / Q000276:immunology*; D050791:STAT Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D037521:Virulence Factors / Q000276:immunology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D000922:Immunotoxins; D020928:Mitogen-Activated Protein Kinases; D017455:Receptors, IgE; D050791:STAT Transcription Factors; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D037521:Virulence Factors; D020741:rho GTP-Binding Proteins; D000097668:Pseudomonas aeruginosa Exotoxin A
keywords: Fcε-PE40; chimeric toxin; colon cancer; mast cell; tumor microenvironment