VSIG4 expression on macrophages facilitates lung cancer development

Liao, Yixiang; Guo, Sheng; Chen, Yongwen; Cao, Dayan; Xu, Huan; Yang, Chengying; Lei, Fei; Ni, Bing; Ruan, Zhihua

doi:10.1038/labinvest.2014.73

Cited by 76 publications

(67 citation statements)

References 34 publications

(37 reference statements)

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“…To date, in vitro and in vivo studies have consistently implicated VSIG4 as a receptor of complement C3 on the surface of macrophages playing a vital role in phagocytosis and the clearance of pathogens in the circulation (Helmy et al, 2006;Vogt et al, 2006). Most studies have focused on the function of VSIG4 in phagocytosis (Gorgani et al, 2011;Broadley et al, 2016;Zeng et al, 2016;Nagre et al, 2018), although several recent studies have found that VSIG4 is associated with tumour progression (Liao et al, 2014;Xu et al, 2015;Byun et al, 2017). Normally, VSIG4 is expressed on resting macrophages and expression is lost upon activation, and VSIG4 hi macrophages plays an anti-inflammatory and immunosuppressive role in vivo (Vogt et al, 2006;Irvine et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Serum soluble VSIG4 as a surrogate marker for the diagnosis of lymphoma‐associated hemophagocytic lymphohistiocytosis

et al. 2020

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Summary Lymphoma‐associated haemophagocytic lymphohistiocytosis (L‐HLH) is characterized by excessively activated macrophages and cytotoxic T lymphocytes, but few reliable markers for activated macrophages are available clinically. This study, designed to discover novel biomarkers for the diagnosis of lymphoma patients with L‐HLH, was initiated between 2016 and 2018. Fifty‐seven adult lymphoma patients were enrolled — 39 without HLH and 18 with HLH. The differential serum protein expression profile was first screened between lymphoma patients with and without L‐HLH by a quantitative mass spectrometric approach. Soluble V‐set and immunoglobulin domain‐containing 4 (sVSIG4), specifically expressed by macrophages, was significantly upregulated in the L‐HLH group. Subsequently, sVSIG4 concentration was confirmed by enzyme‐linked immunosorbent assay to be significantly increased in lymphoma patients with L‐HLH. When it was exploited for the diagnosis of lymphoma patients with L‐HLH, the area under a receiver operating characteristic curve was 0·98 with an optimal cut‐off point of 2195 pg/ml and the corresponding sensitivity and specificity were 94·44% and 94·87% respectively. In addition, the one‐year overall survival was significantly worse in patients with a sVSIG4 concentration above 2195 pg/ml compared with those below 2195 pg/ml (5·3% vs. 72·2%, P < 0·0001). sVSIG4 may be a surrogate marker of activated macrophages for the diagnosis of lymphoma patients with L‐HLH.

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Section: Discussionmentioning

confidence: 99%

Serum soluble VSIG4 as a surrogate marker for the diagnosis of lymphoma‐associated hemophagocytic lymphohistiocytosis

et al. 2020

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“…45 VSIG4 molecules appear to be expressed on the surface of resident macrophages in peripheral tissues including the liver, and they disappear after macrophage activation. 21 Consequently, immature macrophages in local tissues control unwanted immune responses by suppressing T cell activation via VSIG4.…”

Section: Discussionmentioning

confidence: 99%

Extracellular stimulation of VSIG4/complement receptor Ig suppresses intracellular bacterial infection by inducing autophagy

et al. 2016

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VSIG4/CRIg (V-set and immunoglobulin domain containing 4) is a transmembrane receptor of the immunoglobulin superfamily that is expressed specifically on macrophages and mature dendritic cells. VSIG4 signaling accelerates phagocytosis of C3-opsonized bacteria, thereby efficiently clearing pathogens within macrophages. We found that VSIG4 signaling triggered by C3-opsonized Listeria (opLM) or by agonistic anti-VSIG4 monoclonal antibody (mAb) induced macrophages to form autophagosomes. VSIG4-induced autophagosomes were selectively colocalized with the intracellular LM while starvation-induced autophagosomes were not. Consistent with these results, the frequency of autophagosomes induced by infection with opLM was lower in VSIG4-deficient bone marrow-derived macrophages (BMDMs) than in WT BMDMs. Furthermore, when VSIG4 molecules were overexpressed in HeLa cells, which are nonmacrophage cells, VSIG4 triggering led to efficient uptake of LM, autophagosome formation, and killing of the infected LM. These findings suggest that VSIG4 signaling not only promotes rapid phagocytosis and killing of C3-opsonized intracellular bacteria, as previously reported, but also induces autophagosome formation, eliminating the LM that have escaped from phagosomes. We conclude that VSIG4 signaling provides an anti-immune evasion mechanism that prevents the outgrowth of intracellular bacteria in macrophages.

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“…These results support the role of wild-type CALR in the regulation of physiological hematopoiesis enhancing differentiation toward the erythroid and MK lineages. Furthermore, our GEP data pointed out the upregulation of several proinflammatory genes, such as the chemokines CCL2 [25], CCL3 [26], and CXCL5 [27], and cytokines like IL8 [27], and cancer-related markers already described in hematological neoplasms, such as EMP1 [30], VSIG4 [31], and LEP [32].…”

Section: Discussionmentioning

confidence: 99%

“…Functional analysis by means of Ingenuity Pathway analysis software (IPA, version 8.6; Ingenuity Systems, Redwood City, CA, www.ingenuity.com) identified several categories of DEGs, such as platelet aggregation, proinflammation genes, erythrocyte differentiation, and several cancer markers already known in both solid and hematological neoplasms. In particular, among upregulated genes, we found genes involved in platelet activation and aggregation, such as SGK1 [21], CD9 [22], FN1 [23], and THBS1 [24]; genes involved in proinflammatory mechanisms such as chemokines CCL2 [25], CCL3 [26], and CXCL5 [27] and cytokines like IL8 [27]; genes involved in erythrocyte differentiation such as RHCE [28] and HBZ [29]; and several cancer markers already known in both solid and hematological malignancies such as EMP1 [30], VSIG4 [31], and LEP [32] ( Fig. 3B and Supplemntary Fig.…”

Section: Gene Expression Profile Of Calr-overexpressing Cd34 + Cellsmentioning

confidence: 99%

Calreticulin Affects Hematopoietic Stem/Progenitor Cell Fate by Impacting Erythroid and Megakaryocytic Differentiation

Salati

Prudente

Genovese

et al. 2018

Stem Cells and Development

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Calreticulin (CALR) is a chaperone protein that localizes primarily to the endoplasmic reticulum (ER) lumen where it is responsible for the control of proper folding of neo-synthesized glycoproteins and the retention of calcium. Recently, mutations affecting exon 9 of the CALR gene have been described in approximately 40% of patients with myeloproliferative neoplasms (MPNs). Although the role of mutated CALR in the development of MPNs has begun to be clarified, there are still no data available on the function of wild-type (WT) CALR during physiological hematopoiesis. To shed light on the role of WT CALR during normal hematopoiesis, we performed gene silencing and overexpression experiments in hematopoietic stem progenitor cells (HSPCs). Our results showed that CALR overexpression is able to affect physiological hematopoiesis by enhancing both erythroid and megakaryocytic (MK) differentiation. In agreement with overexpression data, CALR silencing caused a significant decrease in both erythroid and MK differentiation of human HSPCs. Gene expression profiling (GEP) analysis showed that CALR is able to affect the expression of several genes involved in HSPC differentiation toward both the erythroid and MK lineages. Moreover, GEP data also highlighted the modulation of several genes involved in ER stress response, unfolded protein response (UPR), and DNA repair, and of several genes already described to play a role in MPN development, such as proinflammatory cytokines and hematological neoplasm-related markers. Altogether, our data unraveled a new and unexpected role for CALR in the regulation of normal hematopoietic differentiation. Moreover, by showing the impact of CALR on the expression of genes involved in several biological processes already described in cellular transformation, our data strongly suggest a more complex role for CALR in MPN development that goes beyond the activation of the THPO receptor and involves ER stress response, UPR, and DNA repair.

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VSIG4 expression on macrophages facilitates lung cancer development

Cited by 76 publications

References 34 publications

Serum soluble VSIG4 as a surrogate marker for the diagnosis of lymphoma‐associated hemophagocytic lymphohistiocytosis

Serum soluble VSIG4 as a surrogate marker for the diagnosis of lymphoma‐associated hemophagocytic lymphohistiocytosis

Extracellular stimulation of VSIG4/complement receptor Ig suppresses intracellular bacterial infection by inducing autophagy

Calreticulin Affects Hematopoietic Stem/Progenitor Cell Fate by Impacting Erythroid and Megakaryocytic Differentiation

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