Tumour-Associated Macrophages (TAMs) in Colon Cancer and How to Reeducate Them

Yahaya, Muhamad Afiq Faisal; Lila, Mohd Azmi Mohd; Ismail, Saila; Zainol, Murizal; Afizan, N. A. R. Nik Mohd

doi:10.1155/2019/2368249

Cited by 142 publications

(129 citation statements)

References 87 publications

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“…6b). Macrophages are the main cell types secreting TNF and therefore involved in tumor formation in CRC [33]. To further understand the role of ELN in regulating tumor development in CRC, we isolated BMDM from mice with over 96% purity (Fig.…”

Section: Tnf Gene Expression Is Increased In Crc Patients and Eln Indmentioning

confidence: 99%

Elastin is a key factor of tumor development in colorectal cancer

Jiang

et al. 2020

BMC Cancer

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Background: Colorectal cancer (CRC) is the most common cancer and a leading cause of death worldwide. Extracellular matrix (ECM) proteins regulate tumor growth and development in CRC. Elastin (ELN) is a component of ECM proteins involved in the tumor microenvironment. However, the role of ELN in CRC remains unclear. Methods: In this study, we analyzed ELN gene expression in tumors from CRC patients and adjacent non-tumor colon tissues and healthy controls from two existing microarray datasets. ELN protein was measured in human normal colon cells and colon cancer epithelial cells and tumor development was assessed in colon epithelial cells cultured in medium with or without ELN peptide on plates coated with ELN recombinant protein. Control plates were coated with PBS only. Results: We found ELN gene expression was increased in tumors from CRC patients compared to adjacent nontumor tissues and healthy controls. ELN protein was increased in cancer cells compared to normal colon epithelial cells. Transforming growth factor beta (TGF-β) was a key cytokine to induce production of ECM proteins, but it did not induce ELN expression in colon cancer cells. Matrix metalloproteinase 9 (MMP9) gene expression was increased, but that of MMP12 (elastase) did not change between CRC patients and control. Tissue inhibitor of metalloproteinases 3 (TIMP3) gene expression was decreased in colon tissues from CRC patients compared to healthy controls. However, MMP9, MMP12 and TIMP3 proteins were increased in colon cancer cells. ELN recombinant protein increased proliferation and wound healing in colon cancer epithelial cells. This had further increased in cancer cells incubated in plates coated with recombinant ELN coated plate and in culture media containing ELN peptide. A potential mechanism was that ELN induced epithelial mesenchymal transition with increased alpha-smooth muscle actin and vimentin proteins but decreased E-cadherin protein. Tumor necrosis factor alpha (TNF) mRNA was also increased in CRC patients compared to controls. ELN recombinant protein induced further increases in TNF protein in mouse bone marrow derived macrophages after lipopolysaccharide stimulation. Conclusions: These data suggest ELN regulates tumor development and the microenvironment in CRC.

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Section: Tnf Gene Expression Is Increased In Crc Patients and Eln Indmentioning

confidence: 99%

Elastin is a key factor of tumor development in colorectal cancer

Jiang

et al. 2020

BMC Cancer

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“…However, a new hypothesis assumes that macrophages in vivo do not strictly follow the M1/M2 model, but rather tend to switch from one type to the other depending on the microenvironment activating signal they receive [26]. This being said, it is considered inappropriate to classify tumor-associated macrophages into either M1 or M2 type, but rather to consider them as a heterogeneous population playing different roles at different stages of tumor development [27][28][29][30]. Again, this may explain the discrepancy in the results of macrophages of different studies focusing on the prognostic role of macrophage in CRC including ours.…”

Section: Discussionmentioning

confidence: 99%

Study of Tumor Microenvironment and Host Response in Colorectal Cancer: Immunohistochemical and Clinicopathological Approach

Raffalla

Helal

El-Latif

et al. 2019

Asian J Pharm Clin Res

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Objective: This study aimed to evaluate the immunohistochemical expression of forkhead boxP3 (Foxp3), CD8, CD68, and CD21 in stroma between tumor cells of colorectal cancer (CRC) patients and examines the relationship between these variables and clinicopathological parameter and patients’ prognosis. Methods: In this work, 50 cases of colorectal carcinomas were included and immunohistochemical evaluation of Foxp3, CD8, CD68, and CD21 in tumor tissue samples. Results: Tumor-infiltrating lymphocytes (TILs) including cytotoxic T cells and regulatory T cells as well as tumor-associated macrophages and follicular dendritic cells (FDCs) were studied in the stroma of the tumor using immunostaining technique for CD8, Foxp3, CD68, and CD21, respectively. Cases were followed up. CD8-positive cytotoxic T cells, Foxp3-positive regulatory T cells, and CD21 positive-FDCs were significantly more pronounced in early tumors and those with longer overall survival. On the other hand, CD68 positive macrophages were more encountered in late stage and metastatic tumors as well as tumors with shorter overall survival, but these results not reached the level of significance. Conclusion: We concluded that (TILs) and FDCs are conferring better prognosis in CRCs, they may act synergistically in stimulating a protective immune response in the tumor microenvironment that hinders tumor progression, while the role of tumor-associated macrophages in CRCs is still controversial and needs further studies.

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“…In addition to their role in both innate and adaptive immunity, research has shown that macrophages also play a dynamic role in the body by interacting with immune cells and epithelial cells to regulate the cellular environment through secretion of cytokines and chemokines [1][2][3][4]. Furthermore, studies on various cancers have revealed that macrophages participate in tumor initiation and development, especially the M2 subtype of macrophages [5][6][7][8][9][10]. A comprehensive understanding of macrophage polarization/subtypes and their function in cellular signaling will not only advance our current knowledge on these multifaceted macrophages but also shed light on how to target them for a cancer therapy purpose.…”

Section: Introductionmentioning

confidence: 99%

Signaling of Macrophages that Contours the Tumor Microenvironment for Promoting Cancer Development

Messex

Byrd

Liou

2020

Cells

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The immune response is critical in the maintenance of an organism's health. The immune response can be broken down into two groups. The innate response, which is fast-acting and rids the body of most foreign material before infection occurs, and the adaptive response, a more specific defense against pathogen composed mostly of antibody production and killer cells. Linking the two responses via cytokine and chemokine secretion are macrophages, motile phagocytic cells that ingest and present foreign material playing a role in the innate and adaptive immune response. Although macrophages are necessary for the survival of an organism, studies have also shown macrophages play a more sinister role in the initiation, progression, and metastasis in tumorous cells. In this comprehensive review, we show how macrophages induce such a response through abnormal cellular signaling and creating a cellular microenvironment conducive for tumor growth and metastasis, as well as the future outlook of this field.

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Tumour-Associated Macrophages (TAMs) in Colon Cancer and How to Reeducate Them

Cited by 142 publications

References 87 publications

Elastin is a key factor of tumor development in colorectal cancer

Elastin is a key factor of tumor development in colorectal cancer

Study of Tumor Microenvironment and Host Response in Colorectal Cancer: Immunohistochemical and Clinicopathological Approach

Signaling of Macrophages that Contours the Tumor Microenvironment for Promoting Cancer Development

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