title: S100A8 facilitates the migration of colorectal cancer cells through regulating macrophages in the inflammatory microenvironment.
abstract: Previous studies have shown that S100 calcium-binding protein A8 (S100A8) contributes to the survival and migration of colorectal cancer (CRC) cells. However, whether S100A8 participates in the progression and metastasis of CRC via the regulation of macrophages in the tumor inflammatory microenvironment remains unknown. In this study, phorbol myristate acetate (PMA) was used to induce the differentiation of THP-1 monocytes to macrophages. MTT assay, western blot analysis, immunofluorescence staining, semi-quantitative RT-PCR (semi-PCR), quantitative real-time PCR (qPCR), Gaussia luciferase activity assay and ELISA were performed to analyze the roles and molecular mechanisms of S100A8 in the modulation of macrophages. MTT assay, flow cytometric analysis, Hoechst staining, wound healing and Transwell migration assay were used to test the effect of S100A8 on the viability and migration of CRC cells co-cultured with macrophages in the inflammatory microenvironment. We found that THP-1 monocytes were induced by PMA and differentiated to macrophages. S100A8 activated the NF-κB pathway in the macrophages and promoted the expression of miR-155 and inflammatory cytokines IL-1β and TNF-α in the inflammatory microenvironment mimicked by lipopolysaccharides (LPS). Furthermore, S100A8 contributed to augment the migration but not the viability of the CRC cells co-cultured with the macrophages in the inflammatory microenvironment. Altogether, our study demonstrated that S100A8 facilitated the migration of CRC cells in the inflammatory microenvironment, and the underlying molecular mechanisms may be partially attributed to the overexpression of miR-155, IL-1β and TNF-α through activation of the NF-κB pathway in macrophages.
authors.affiliation: Key Laboratory of Clinical Diagnosis, Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: He
authors.initials: H
authors.lastname: Zha
authors.affiliation: Key Laboratory of Clinical Diagnosis, Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.affiliation: Key Laboratory of Clinical Diagnosis, Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Xueru
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Duan
authors.affiliation: Key Laboratory of Clinical Diagnosis, Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Aifang
authors.initials: A
authors.lastname: Li
authors.affiliation: Key Laboratory of Clinical Diagnosis, Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Key Laboratory of Clinical Diagnosis, Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Zongyue
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Clinical Diagnosis, Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Clinical Diagnosis, Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Jiaqing
authors.initials: J
authors.lastname: Xie
authors.affiliation: Key Laboratory of Clinical Diagnosis, Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Shimei
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Clinical Diagnosis, Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Huan
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Clinical Diagnosis, Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhou
mesh_terms: D040501:Calgranulin A / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D018920:Coculture Techniques / Q000379:methods; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D045325:HCT116 Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D059016:Tumor Microenvironment / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D040501:Calgranulin A; D053583:Interleukin-1beta; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha