M-CSF cooperating with NFκB induces macrophage transformation from M1 to M2 by upregulating c-Jun

Yang, Yujiao; Qin, Jianjie; Lan, Lan; Li, Ning; Wang, Chengfang; He, Pengfei; Liu, Fang; Hóng, Ní; Wang, Yue

doi:10.4161/cbt.26718

Cited by 57 publications

(56 citation statements)

References 29 publications

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“…It has been reported by other groups that IL-6, M-CSF, CCL2 and PDGF-B were significantly upregulated in M2 macrophages in vitro or in vivo. 3,11,16 These data were in part accord with our current conclusions.…”

Section: Discussionsupporting

confidence: 82%

“…Paraffin-embedded and formalin-fixed samples were cut into 5mm sections, and then processed for immunohistochemistry as previously described. 16 Following incubation with anti-CD68 antibody (Ab, Boster, Wuhan, China) and anti-PTEN Ab (Bioworld, Shanghai, China), immunoactivity was detected with diaminobenzidine (DAB). For immunofluorescence analysis, the treated cells were fixed and then perforated with 0.5% Triton X-100, and then were blocked for 1 h prior to staining with rabbit anti-PTEN Ab (1:200), anti-p-PTEN Ab (1:200), rabbit anti-NHERF1 Ab (1:300) (Cell Signaling Technology, Beijing, China) for overnight at 4 degrees Celsius.…”

Section: Immunohistochemical and Immunofluorescence Analysesmentioning

confidence: 99%

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PTEN inhibits macrophage polarization from M1 to M2 through CCL2 and VEGF-A reduction and NHERF-1 synergism

Li¹,

Qin

Lan³

et al. 2015

Cancer Biology & Therapy

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PTEN has been studied in several tumor models as a tumor suppressor. In this study, we explored the role of PTEN in the inhibition state of polarized M2 subtype of macrophage in tumor microenvironment (TME) and the underlying mechanisms. To elucidate the potential effect in TME, RAW 264.7 macrophages and 4T1 mouse breast cancer cells were co-cultured to reconstruct tumor microenvironment. After PTEN was down-regulated with shRNA, the expression of CCL2 and VEGF-A, which are definited to promote the formation of M2 macrophages, have a dramatically increase on the level of both gene and protein in co-cultured RAW 264.7 macrophages. And at the same time, NHERF-1 (Na C /H C exchanger regulating factor-1), another tumor suppressor has a similar tendency to PTEN. Q-PCR and WB results suggested that PTEN and NHERF-1 were consistent with one another no matter at mRNA or protein level when exposed to the same stimulus. Coimmunoprecipitation and immunofluorescence techniques confirmed that PTEN and NHERF-1 were coprecipitated, and NHERF-1 protein expression was properly reduced with rCCL2 effect. In addition, cell immunofluorescence images revealed a profound transferance, in co-cultured RAW 264.7 macrophages, an up-regulation of NHERF-1 could promote the PTEN marked expression on the cell membrane, and this form for the interaction was not negligible. These observations illustrate PTEN with a certain synergy of NHERF-1, as well as down-regulation of CCL2 suppressing M2 macrophage transformation pathway. The results suggest that the activation of PTEN and NHERF-1 may impede the evolution of macrophages beyond the M1 into M2 phenotype in tumor microenvironment.

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Section: Discussionsupporting

confidence: 82%

Section: Immunohistochemical and Immunofluorescence Analysesmentioning

confidence: 99%

PTEN inhibits macrophage polarization from M1 to M2 through CCL2 and VEGF-A reduction and NHERF-1 synergism

Li¹,

Qin

Lan³

et al. 2015

Cancer Biology & Therapy

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“…Pollard et al showed, that primary inflammatory macrophages change in tumor from phenotype to macrophages similar to those that play a role in the regulation of tissue formation during development [38]. Later formed M2/trophic type macrophages expressing less iNOS and TNF-γ are formed by blockage of NFkB transcription factor due to p50 homodimers leading to a weaker immune reaction [41][42][43]. Induction of M2 macrophages and their tumor cell interaction have recently been investigated in PC by Partecke et al [44].…”

Section: Discussionmentioning

confidence: 95%

The lymphocyte to monocyte ratio in peripheral blood represents a novel prognostic marker in patients with pancreatic cancer

Stotz¹,

Szkandera

Stojaković

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…26 In addition, M-CSF, a secreted cytokine derived from various cells, is known to be a crucial regulator for the differentiation, recruitment, and polarization of macrophages. 17,18 Therefore, we were intrigued to speculate that hypoxia-induced ATF4 may promote progression of proliferating IH through recruitment of macrophages into tumor tissues via induction of M-CSF. To test this hypothesis, we first evaluated the expression of M-CSF and its association with ATF4 at different stages of IHs.…”

Section: Discussionmentioning

confidence: 99%

“…15 Macrophage colony-stimulating factor (M-CSF) is a wellknown key regulator for the differentiation, polarization, and survival of macrophages among a broad spectrum of pathologies. [16][17][18] However, whether hypoxia, a wellestablished driving force in IH progression, may affect or regulate macrophages in IH remains largely unknown. Besides, how the infiltration of M2-polarized macrophages in proliferating IH is modulated is still far from clear.…”

mentioning

confidence: 99%

Association of ATF4 Expression With Tissue Hypoxia and M2 Macrophage Infiltration in Infantile Hemangioma

Xia

Zhu

Wang

et al. 2017

J Histochem Cytochem.

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SummaryAccumulating studies have revealed the hypoxic condition and its crucial role in the distinctive progression of infantile hemangioma (IH), the most common benign tumor in infancy. Activating transcription factor 4 (ATF4), an important gene mediating cellular adaptation to various stress signals, could confer a survival advantage for tumor cells under hypoxia and regulate tumor progression. However, the potential role of ATF4 in IH was still unknown. In this study, the expression of hypoxia inducible factor (HIF)-1α, ATF4, and macrophage colony-stimulating factor (M-CSF) in 27 specimens of IH was measured by immunochemistry and double-labeling immunofluorescence, followed by the Spearman rank correlation test. Our results showed that the expression of HIF-1α, ATF4, and M-CSF was significantly upregulated in proliferating IH compared with involuting IH. Meanwhile, HIF-1α and ATF4, in parallel with ATF4 and M-CSF, exhibited positive correlation and synchronous expression. In addition, our in vitro studies demonstrated that hypoxia obviously upregulated the expression of HIF-1α, ATF4, and M-CSF in hemangioma stem cells. Most importantly, their expression was uniformly correlated with the percentage of M2-polarized macrophages in IH. All those results and established evidence indicated that hypoxia-induced ATF4 expression may promote progression of proliferating IH through M-CSF-induced M2-polarized macrophages infiltration. (J Histochem Cytochem 65:285-294, 2017)

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M-CSF cooperating with NFκB induces macrophage transformation from M1 to M2 by upregulating c-Jun

Cited by 57 publications

References 29 publications

PTEN inhibits macrophage polarization from M1 to M2 through CCL2 and VEGF-A reduction and NHERF-1 synergism

PTEN inhibits macrophage polarization from M1 to M2 through CCL2 and VEGF-A reduction and NHERF-1 synergism

The lymphocyte to monocyte ratio in peripheral blood represents a novel prognostic marker in patients with pancreatic cancer

Association of ATF4 Expression With Tissue Hypoxia and M2 Macrophage Infiltration in Infantile Hemangioma

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