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BMP-6 in Renal Cell Carcinoma Promotes Tumor Proliferation through IL-10–Dependent M2 Polarization of Tumor-Associated Macrophages

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TLDR
It is reported that BMP-6 promotes the growth of RCC by interleukin (IL)-10-mediated M2 polarization of tumor-associated macrophages (TAM) and regulates M1 polarization of TAMs in RCC.
Abstract
Dysregulated bone morphogenetic proteins (BMP) may contribute to the development and progression of renal cell carcinoma (RCC). Herein, we report that BMP-6 promotes the growth of RCC by interleukin (IL)-10-mediated M2 polarization of tumor-associated macrophages (TAM). BMP-6-mediated IL-10 expression in macrophages required Smad5 and STAT3. In human RCC specimens, the three-marker signature BMP-6/IL-10/CD68 was associated with a poor prognosis. Furthermore, patients with elevated IL-10 serum levels had worse outcome after surgery. Together, our results suggest that BMP-6/macrophage/IL-10 regulates M2 polarization of TAMs in RCC.

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M2-polarized tumor-associated macrophages promoted epithelial–mesenchymal transition in pancreatic cancer cells, partially through TLR4/IL-10 signaling pathway

TL;DR: Investigation of the roles of M2-polarized TAMs and TLR4/IL-10 signaling in the EMT of Panc-1 and BxPC-3 pancreatic cancer cell lines showed increased fibroblastic morphology, upregulated mesenchymal markers vimentin and snail at the mRNA and protein levels, and increased proliferation, migration, and metalloproteinase (MMP)2 and MMP9 proteolytic activity in pancreaticcancer cells
Journal ArticleDOI

Immunoregulation by members of the TGFβ superfamily

TL;DR: The signalling pathways of the TGFβ superfamily are outlined and new insights into the immunoregulatory functions of BMPs and activins in the context of infection, inflammation and cancer are discussed.
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Exosomes derived from hypoxic epithelial ovarian cancer cells deliver microRNAs to macrophages and elicit a tumor-promoted phenotype

TL;DR: It is revealed that under hypoxic conditions, EOC cell-derived exosomes deliver miRNAs to induce M2 macrophage polarization, which promotes E OC cell proliferation and migration.
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Lessons from patient-derived xenografts for better in vitro modeling of human cancer.

TL;DR: By mimicking crucial in vivo characteristics through use of 3D cultures, co-culture systems and acidic culture conditions, an in vitro cancer model/microenvironment that is more physiologically relevant may be engineered to produce results more readily applicable to the clinic.
References
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Inflammation and cancer

TL;DR: It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration.
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Cancer statistics, 2010

TL;DR: The American Cancer Society as mentioned in this paper estimated the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data regarding cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from National Center for Health Statistics.
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Interleukin-10 and the interleukin-10 receptor.

TL;DR: Findings that have advanced the understanding of IL-10 and its receptor are highlighted, as well as its in vivo function in health and disease.
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Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes

TL;DR: These functionally polarized cells, and similarly oriented or immature dendritic cells present in tumors, have a key role in subversion of adaptive immunity and in inflammatory circuits that promote tumor growth and progression.
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Macrophage activation and polarization.

TL;DR: The main functions of polarized macrophages are reviewed and the perspectives of this field are discussed, which include high endocytic clearance capacities and trophic factor synthesis, accompanied by reduced pro-inflammatory cytokine secretion.
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