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The soluble glycoprotein NMB (GPNMB) produced by macrophages induces cancer stemness and metastasis via CD44 and IL-33

Liguori, M ; Digifico, E ; Vacchini, A ; Avigni, R ; Colombo, F S ; Borroni, E M ; Farina, F M ; Milanesi, S ; Castagna, A ; Mannarino, L ; Craparotta, I ; Marchini, S ; Erba, E ; Panini, N ; Tamborini, M ; Rimoldi, V ; Allavena, P ; Belgiovine, C

Cellular & molecular immunology, 2021-03, Vol.18 (3), p.711-722 [Periódico revisado por pares]

China: Nature Publishing Group

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Título:
The soluble glycoprotein NMB (GPNMB) produced by macrophages induces cancer stemness and metastasis via CD44 and IL-33
Autor: Liguori, M ; Digifico, E ; Vacchini, A ; Avigni, R ; Colombo, F S ; Borroni, E M ; Farina, F M ; Milanesi, S ; Castagna, A ; Mannarino, L ; Craparotta, I ; Marchini, S ; Erba, E ; Panini, N ; Tamborini, M ; Rimoldi, V ; Allavena, P ; Belgiovine, C
Assuntos: Animal models ; Animals ; Apoptosis ; Cancer ; CD44 antigen ; Cell Proliferation ; Cell survival ; Fibrosarcoma - etiology ; Fibrosarcoma - metabolism ; Fibrosarcoma - pathology ; Gene Expression Regulation, Neoplastic ; Glycoproteins ; Humans ; Hyaluronan Receptors - genetics ; Hyaluronan Receptors - metabolism ; Interleukin 1 receptors ; Interleukin-33 - genetics ; Interleukin-33 - metabolism ; Lung Neoplasms - etiology ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Macrophages ; Macrophages - immunology ; Male ; Membrane Glycoproteins - genetics ; Membrane Glycoproteins - metabolism ; Metastases ; Metastasis ; Mice ; Mice, Inbred DBA ; Myeloid cells ; Neoplastic Stem Cells - immunology ; Neoplastic Stem Cells - metabolism ; Neoplastic Stem Cells - pathology ; Paracrine signalling ; Phenotypes ; Sarcoma, Experimental - etiology ; Sarcoma, Experimental - metabolism ; Sarcoma, Experimental - pathology ; Spheroids ; Stem cell transplantation ; Stem cells ; Tumor cells ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays
É parte de: Cellular & molecular immunology, 2021-03, Vol.18 (3), p.711-722
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: 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.
Editor: China: Nature Publishing Group
Idioma: Inglês

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The soluble glycoprotein NMB (GPNMB) produced by macrophages induces cancer stemness and metastasis via CD44 and IL-33

Liguori, M ; Digifico, E ; Vacchini, A ; Avigni, R ; Colombo, F S ; Borroni, E M ; Farina, F M ; Milanesi, S ; Castagna, A ; Mannarino, L ; Craparotta, I ; Marchini, S ; Erba, E ; Panini, N ; Tamborini, M ; Rimoldi, V ; Allavena, P ; Belgiovine, C

China: Nature Publishing Group

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