Background: Tumor environment has been recognized to affect cancer cell progression, such as tumor-associated macrophages. However, increasing evidences suggest that tumor cells are capable of regulating polarization of tumor-associated macrophages. In this study, we investigate the mechanism of how colon cancer cell impacts tumor-associated macrophages polarization. Methods: We employed flow cytometry to detect marker molecules on macrophage membrane, such as CD68, CD16, and CD204. In addition, we used enzyme-linked immunosorbent assay to examine the level of these cytokines (interleukin-6, interleukin-1β, interleukin-10, and Arginase-1) secreted by colon cancer cells into the culture medium. Western blot was utilized to probe downstream proteins of epidermal growth factor receptor (EGFR)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Results: We cocultured colon cancer cell lines (HCT8 or HCT116) with human myeloid leukemia mononuclear cells (THP-1) and found that interleukin-6 and interleukin-1β levels were reduced, and instead, interleukin-10 and Arginase-1 levels were elevated, suggesting that colon cancer cells contributed to M2 polarization of THP-1. Meanwhile, high level of various growth factors (transforming growth factor-β [TGF-β], epidermal growth factor [EGF], and hepatocyte growth factor [HGF]) was observed in the medium of THP-1 cocultured with colon cancer cells. Furthermore, the protein level of phosphorylated PI3K, AKT, and mTOR significantly increased in THP-1 cell cocultured with colon cancer cells compared to THP-1 group. Besides, we established that colon cancer cells exerted their stimulatory effect on M2 polarization of macrophage from monocyte THP-1 using EGFR antibody mAb225 and PI3K inhibitor LY294002. Conclusion: We provide evidence that EGF which are secreted by colon cancer cells play contributory role in M2 polarization of macrophages, which support the notion that tumor environment, including tumor-associated macrophages, can be targeted to develop effective strategies for treating cancer.
Cancer remains one of the most common causes of mortality globally. Chemotherapy, one of the major treatment strategies for cancer, primarily functions by targeting the cancer cells and affecting them physiologically, but also affects normal cells, which is a major concern at present. Therefore, adverse effects of chemotherapy drugs, including myelosuppression and liver and kidney damage, are of concern. Now, microbial products have attracted attention in cancer treatment research. Notably, carcinogenesis is considered to be associated with microbial dysbiosis, particularly the positive antitumor effects of bifidobacteria. Although there remains a substantial amount to be understood about the regulation of bifidobacteria, bifidobacteria remain an attractive and novel source of cancer therapeutics. The present review focuses on introducing the latest information on the antitumor effects of bifidobacteria and to propose future strategies for using bifidobacteria in the development of cancer therapeutics.
Background
Faecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium difficile infections and chronic gastrointestional infections. However, the risks of FMT and the selection process of suitable donors remain insufficiently characterized. The eligibility rate for screening, underlying microbial basis, and core ethical issues of stool donors for FMT are yet to be elucidated in China.
Results
The potential stool donors were screened from December 2017 to December 2019 with the help of an online survey, clinical assessments, and stool and blood testing. Bioinformatics analyses were performed, and the composition and stability of gut microbiota in stool obtained from eligible donors were dynamically observed using metagenomics. Meanwhile, we build a donor microbial evaluation index (DoMEI) for stool donor screening. In the screening process, we also focused on ethical principles and requirements. Of the 2071 participants, 66 donors were selected via the screening process (3.19% success rate). Although there were significant differences in gut microbiota among donors, we found that the changes in the gut microbiota of the same donor were typically more stable than those between donors over time.
Conclusions
DoMEI provides a potential reference index for regular stool donor re-evaluation. In this retrospective study, we summarised the donor recruitment and screening procedure ensuring the safety and tolerability for FMT in China. Based on the latest advances in this field, we carried out rigorous recommendation and method which can assist stool bank and clinicians to screen eligible stool donor for FMT.
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