期刊
CELLULAR & MOLECULAR IMMUNOLOGY
卷 18, 期 3, 页码 711-722出版社
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/s41423-020-0501-0
关键词
cancer stem cells; GPNMB; IL-33; metastasis; tumor associated macrophages
类别
资金
- Italian Association for Cancer Research (AIRC)
- Italian Ministry of Health [GR-201302356521]
- AIRC
The study reveals a new paracrine axis, GPNMB and IL-33, that is activated during the cross talk between macrophages and tumor cells, eventually promoting cancer cell survival, the expansion of cancer stem cells, and the acquisition of a metastatic phenotype.
In cancer, myeloid cells have tumor-supporting roles. We reported that the protein GPNMB (glycoprotein nonmetastatic B) was profoundly upregulated in macrophages interacting with tumor cells. Here, using mouse tumor models, we show that macrophage-derived soluble GPNMB increases tumor growth and metastasis in Gpnmb-mutant mice (DBA/2J). GPNMB triggers in the cancer cells the formation of self-renewing spheroids, which are characterized by the expression of cancer stem cell markers, prolonged cell survival and increased tumor-forming ability. Through the CD44 receptor, GPNMB mechanistically activates tumor cells to express the cytokine IL-33 and its receptor IL-1R1L. We also determined that recombinant IL-33 binding to IL-1R1L is sufficient to induce tumor spheroid formation with features of cancer stem cells. Overall, our results reveal a new paracrine axis, GPNMB and IL-33, which is activated during the cross talk of macrophages with tumor cells and eventually promotes cancer cell survival, the expansion of cancer stem cells and the acquisition of a metastatic phenotype.
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