The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Gastric cancer-derived mesenchymal stromal cells trigger M2 macrophage polarization that promotes metastasis and EMT in gastric cancer
Open accessAbstract
Resident macrophages in the tumor microenvironment exert a dual role in tumor progression. So far, the mechanism of intratumoral macrophage generation is still largely unknown. In the present study, the importance of macrophages in the pro-tumor role of gastric cancer-derived mesenchymal stromal cells (GC-MSCs) was observed in a mouse xenograft model with macrophage depletion. In gastric cancer tissues, high expression levels of Ym-1, Fizz-1, arginase-1, and CCR-2, as well as a low expression level of iNOS, were verified, and co-localization of GC-MSCs and tumor-associated macrophages (TAMs) was observed by dual immunofluorescence histochemistry. TAMs isolated from gastric cancer tissues predominantly displayed an M2 phenotype. In a co-culture system, the contribution of GC-MSCs to M2 polarization of macrophages was confirmed by the M2-related protein expression, M2-like immunophenotype and cytokine profile of GC-MSC-primed macrophages in vitro. Blockade of IL-6/IL-8 by neutralizing antibodies significantly attenuated the promoting effect of GC-MSCs on M2-like macrophage polarization via the JAK2/STAT3 signaling pathway. In addition, GC-MSC-primed macrophages promoted the migration and invasion of gastric cancer cells, and the process of EMT in gastric cancer cells was significantly enhanced by GC-MSC-primed macrophage treatment. Our study showed that tumor-promoting GC-MSCs contribute to M2 macrophage polarization within the gastric cancer niche through considerable secretion of IL-6 and IL-8. These GC-MSC-primed macrophages can subsequently prompt gastric cancer metastasis via EMT promotion in gastric cancer cells.
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1 retracted
Ning, Y., Feng, W., Cao, X., Ren, K., Quan, M., Chen, A., Xu, C., Qiu, Y., Cao, J., Li, X., et al. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-018-1010-1 · Cited by 60
RetractedRooijen, N. V., & Sanders, A. (1994) · Journal of Immunological Methods · doi:10.1016/0022-1759(94)90012-4 · Cited by 1,779
Targeting tumor-associated macrophages in cancer
Pathria, P., Louis, T. L., & Varner, J. A. (2019) · Trends in Immunology · doi:10.1016/j.it.2019.02.003 · Cited by 933
Role of EMT in Metastasis and Therapy Resistance
Smith, B., & Bhowmick, N. (2016) · Journal of Clinical Medicine · doi:10.3390/jcm5020017 · Cited by 484
Liu, C.-Y., Xu, J.-Y., Shi, X.-Y., Huang, W., Ruan, T.-Y., Xie, P., & Ding, J.-L. (2013) · Laboratory Investigation · doi:10.1038/labinvest.2013.69 · Cited by 465
Ren, G., Zhao, X., Wang, Y., Zhang, X., Chen, X., Xu, C., Yuan, Z.-R., Roberts, A. I., Zhang, L., Zheng, B., et al. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.08.013 · Cited by 361
Self-citationStromal Cells in the Tumor Microenvironment
Denton, A. E., Roberts, E. W., & Fearon, D. T. (2018) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-78127-3_6 · Cited by 306
Yamaguchi, T., Fushida, S., Yamamoto, Y., Tsukada, T., Kinoshita, J., Oyama, K., Miyashita, T., Tajima, H., Ninomiya, I., Munesue, S., et al. (2016) · Gastric Cancer · doi:10.1007/s10120-015-0579-8 · Cited by 277
Zhang, X., Hu, F., Li, G., Li, G., Yang, X., Liu, L., Zhang, R., Zhang, B., & Feng, Y. (2018) · Cell Death & Disease · doi:10.1038/s41419-017-0176-3 · Cited by 243
Self-citationEchizen, K., Hirose, O., Maeda, Y., & Oshima, M. (2016) · Cancer Science · doi:10.1111/cas.12901 · Cited by 238
Cited by
Lactate metabolism in human health and disease
Li, X., Yang, Y., Zhang, B., Lin, X., Fu, X., An, Y., Zou, Y., Wang, J.-X., Wang, Z., & Yu, T. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01151-3 · Cited by 1,454
Targeting the tumor stroma for cancer therapy
Xu, M., Zhang, T., Xia, R., Wei, Y., & Wei, X. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01670-1 · Cited by 319
Advances in the role of STAT3 in macrophage polarization
Xia, T., Zhang, M., Lei, W., Yang, R., Fu, S., Fan, Z., Yang, Y., & Zhang, T. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1160719 · Cited by 284
The Macrophage Response Is Driven by Mesenchymal Stem Cell-Mediated Metabolic Reprogramming
Luque-Campos, N., Bustamante-Barrientos, F. A., Pradenas, C., García, C., Araya, M. J., Bohaud, C., Contreras-López, R., Elizondo-Vega, R., Djouad, F., Luz-Crawford, P., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.624746 · Cited by 82
Mesenchymal stromal cells as cancer promoters
Antoon, R., Overdevest, N., Saleh, A. H., & Keating, A. (2024) · Oncogene · doi:10.1038/s41388-024-03183-1 · Cited by 75
Metadata
- Authors
- Li, W., Zhang, X., Wu, F., Zhou, Y., Bao, Z., Li, H., Zheng, P., & Zhao, S.
- Venue
- Cell Death & Disease
- Published
- 2019-12-04
- Volume
- 10
- Issue
- 12
- Pages
- 918-918
- ISSN
- 2041-4889 (ISSN-L)
- OpenAlex
- W2992471949
- Cited by
- 359
- References
- 36
- FWCI
- 12.66
- Type
- journal article
- Language
- en
- Open access
- gold
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- Li, W., Zhang, X., Wu, F., Zhou, Y., Bao, Z., Li, H., Zheng, P., & Zhao, S. (2019). Gastric cancer-derived mesenchymal stromal cells trigger M2 macrophage polarization that promotes metastasis and EMT in gastric cancer. Cell Death & Disease. https://doi.org/10.1038/s41419-019-2131-y
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