The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
M1-like tumor-associated macrophages activated by exosome-transferred THBS1 promote malignant migration in oral squamous cell carcinoma
Open accessAbstract
BACKGROUND: Treatment strategies targeting tumor-associated macrophages (TAMs) have been proposed in cancer areas. The functional alterations of macrophages in the microenvironment during the tumorigenesis of human epithelial cancer remain poorly understood. Here, we explored phenotypic alteration of macrophages during the development of oral squamous cell carcinoma (OSCC). METHODS: Conditioned media (CM) and exosome supernatants were harvested from normal oral epithelium, oral leukoplakia cells and OSCC cells. We measured phenotypic alteration of macrophages using flow cytometry, luminex assays, and quantitative real-time PCR assay. Intracellular signaling pathway analysis, mass spectrometry proteomics, western blotting, enzyme-linked immunosorbent assay, immunohistochemical staining, and bioinformatics analysis were performed to uncover the underlying mechanisms. RESULTS: THP-1-derived and PBMCs derived macrophages exhibited an M1-like phenotype but not M2-like phenotype, when treated with CM from OSCC cells but not with the CM from normal epithelium or leukoplakia cells. Further investigations revealed that macrophages were activated by taking up exosomes released from OSCC cells through p38, Akt, and SAPK/JNK signaling at the early phase. We further provided evidences that THBS1 derived from OSCC exosomes participated in the polarization of macrophages to an M1-like phenotype. Reciprocally, CM from exosomes induced M1-like TAMs and significantly promoted migration of OSCC cells. CONCLUSIONS: We proposed a novel paracrine loop between cancer cells and macrophages based on exosomes from OSCC. Therefore, target management of M1-like TAMs polarized by exosomes shows great potential as a therapeutic target for the control of cancerous migration in OSCC.
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Cited by
Qi, J., Sun, H., Zhang, Y., Wang, Z., Xun, Z., Li, Z., Ding, X., Bao, R., Hong, L., Jia, W., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29366-6 · Cited by 952
Exosomes in cancer development, metastasis, and immunity
Zhang, L., & Yu, D. (2019) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2019.04.004 · Cited by 870
Shaping Polarization Of Tumor-Associated Macrophages In Cancer Immunotherapy
Gao, J., Liang, Y., & Wang, L. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.888713 · Cited by 555
Roles and mechanisms of exosomal non-coding RNAs in human health and diseases
Li, C., Ni, Y.-Q., Xu, H., Xiang, Q.-Y., Zhao, Y., Zhan, J.-K., He, J.-Y., Li, S., & Liu, Y.-S. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00779-x · Cited by 406
Tumor-derived exosomes in the regulation of macrophage polarization
Baig, M. S., Roy, A., Rajpoot, S., Liu, D., Savai, R., Banerjee, S., Kawada, M., Faisal, S. M., Saluja, R., Saqib, U., et al. (2020) · Inflammation Research · doi:10.1007/s00011-020-01318-0 · Cited by 267
Metadata
- Authors
- Xiao, M., Zhang, J., Chen, W., & Chen, W.
- Venue
- Journal of Experimental & Clinical Cancer Research
- Published
- 2018-07-09
- Volume
- 37
- Issue
- 1
- Pages
- 143-143
- ISSN
- 0392-9078 (ISSN-L)
- 1756-9966
- OpenAlex
- W2827119614
- Cited by
- 256
- References
- 51
- FWCI
- 6.63
- Type
- journal article
- Language
- en
- Open access
- gold
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