Acceleration of tumor growth due to dysfunction in M1 macrophages and enhanced angiogenesis in an animal model of autoimmune disease

Kondo, Takao; Takemoto, Tsunematsu; Yamada, Akiko; Arakaki, Rieko; Saitō, Masako; Otsuka, Kunihiro; Kujiraoka, Satoko; Ushio, Aya; Kurosawa, Mie; Kudo, Yasusei; Ishimaru, Naozumi

doi:10.1038/labinvest.2015.166

Cited by 4 publications

(2 citation statements)

References 56 publications

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“…Pro-inflammatory (M1) TAMs can be cytotoxic to tumor cells [15, 16]. However, M1 TAMs can also contribute to tumor initiation through the mutagenic reactive oxygen and nitrogen species they generate [17, 18].…”

Section: Introductionmentioning

confidence: 99%

Breast cancers from black women exhibit higher numbers of immunosuppressive macrophages with proliferative activity and of crown-like structures associated with lower survival compared to non-black Latinas and Caucasians

Koru‐Sengul

Santander

Mao

et al. 2016

Breast Cancer Res Treat

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Racial disparities in breast cancer incidence and outcome are a major health care challenge. Patients in the black race group more likely present with an early onset and more aggressive disease. The occurrence of high numbers of macrophages is associated with tumor progression and poor prognosis in solid malignancies. Macrophages are observed in adipose tissues surrounding dead adipocytes in “crown-like structures” (CLS). Here we investigated whether the numbers of CD163+ tumor-associated macrophages (TAMs) and/or CD163+ CLS are associated with patient survival and whether there are significant differences across blacks, non-black Latinas, and Caucasians. Our findings confirm that race is statistically significantly associated with the numbers of TAMs and CLS in breast cancer, and demonstrate that the highest numbers of CD163+ TAM/CLS are found in black breast cancer patients. Our results reveal that the density of CD206 (M2) macrophages is a significant predictor of progression-free survival univariately and is also significant after adjusting for race and for HER2, respectively. We examined whether the high numbers of TAMs detected in tumors from black women were associated with macrophage proliferation, using the Ki-67 nuclear proliferation marker. Our results reveal that TAMs actively divide when in contact with tumor cells. There is a higher ratio of proliferating macrophages in tumors from black patients. These findings suggest that interventions based on targeting TAMs may not only benefit breast cancer patients in general but also serve as an approach to remedy racial disparity resulting in better prognosis patients from minority racial groups.

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Section: Introductionmentioning

confidence: 99%

Breast cancers from black women exhibit higher numbers of immunosuppressive macrophages with proliferative activity and of crown-like structures associated with lower survival compared to non-black Latinas and Caucasians

Koru‐Sengul

Santander

Mao

et al. 2016

Breast Cancer Res Treat

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“…It is well known that angiogenesis is correlated with tumor progression and metastasis [ 8 ]. Vascular endothelial growth factor (VEGF), known as a critical angiogenesis factor, could promote tumor development and progression both in vitro and in vivo experiments [ 9 – 11 ]. Meanwhile, tumor-induced angiogenesis and growth could be suppressed by inhibiting VEGF signaling [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Association between vascular endothelial growth factor gene polymorphisms and the risk and prognosis of renal cell carcinoma: A systematic review and meta-analysis

Tang

Qin

et al. 2017

Oncotarget

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The aim of the meta-analysis was to clarify the associations between vascular endothelial growth factor (VEGF) polymorphisms and the risk and prognosis of renal cell carcinoma (RCC). A meta-analysis was performed by searching the databases PubMed, EMBASE and Web of Science for the relevant available studies until August 1st, 2016, and fourteen studies met the inclusion criteria. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of such associations. Besides, the pooled hazard ratios (HRs) with 95% CIs were used to evaluate the overall survival (OS). Fixed- or random-effects models were conducted according to existence of heterogeneity. Publication bias was evaluated using Begg's funnel plots and Egger's regression test. Overall, this meta-analysis included a total of 8,275 patients, who had been accrued between November 2002 and September 2015. Meta-analysis indicated that -2578C/A, +936C/T and +405G/C polymorphisms in the VEGF gene correlated with elevated RCC risk, especially in Asian populations. Moreover, VEGF -1154G/A and -634C/G polymorphisms were found significantly associated with poor OS of RCC. Therefore, this meta-analysis revealed that VEGF -2578C/A, +936C/T, +405G/C polymorphisms were associated with an elevated susceptibility to RCC, indicating that these three polymorphisms might be risk factors for RCC, especially in Asian populations.

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Mesenchymal Stem Cells Direct the Immunological Fate of Macrophages

Luz‐Crawford¹,

Jørgensen²,

Djouad³

2017

Results and Problems in Cell Differentiation

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Mesenchymal stem cells (MSC) are multipotent stem cells with a broad well-described immunosuppressive potential. They are able to modulate both the innate and the adaptive immune response. Particularly, MSC are able to regulate the phenotype and function of macrophages that are critical for different biological processes including wound healing, inflammation, pathogenesis of several autoimmune diseases, and tumor growth. These multifunctional roles of macrophages are due to their high plasticity, which enable them to adopt different phenotypes such as a pro-inflammatory M1 and anti-inflammatory M2 phenotype. MSC promote macrophage differentiation toward an M2-like phenotype with a high tissue remodeling potential and anti-inflammatory activity but also a pro-tumorigenic function. MSC regulatory effect on macrophages is mediated through the secretion of different immunomodulatory molecules such as PGE, IL1RA, and IL-6. Moreover, the presence of macrophages in damaged tissue and inflammation is essential for MSC to exert their therapeutic function. In this chapter, we discuss how the interplay between macrophages and MSC mutually modulates their phenotypes and functions, orchestrates tissue repair, and controls inflammation during autoimmunity and tumor growth.

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Acceleration of tumor growth due to dysfunction in M1 macrophages and enhanced angiogenesis in an animal model of autoimmune disease

Cited by 4 publications

References 56 publications

Breast cancers from black women exhibit higher numbers of immunosuppressive macrophages with proliferative activity and of crown-like structures associated with lower survival compared to non-black Latinas and Caucasians

Breast cancers from black women exhibit higher numbers of immunosuppressive macrophages with proliferative activity and of crown-like structures associated with lower survival compared to non-black Latinas and Caucasians

Association between vascular endothelial growth factor gene polymorphisms and the risk and prognosis of renal cell carcinoma: A systematic review and meta-analysis

Mesenchymal Stem Cells Direct the Immunological Fate of Macrophages

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