Estrogen receptor α promotes lung cancer cell invasion via increase of and cross‐talk with infiltrated macrophages through the CCL2/CCR2/MMP9 and CXCL12/CXCR4 signaling pathways

He, Miao; Yu, Wei; Chang, Chawnshang; Miyamoto, Hiroshi; Liu, Xiaohong; Jiang, Ke; Yeh, Shuyuan

doi:10.1002/1878-0261.12701

Cited by 35 publications

(18 citation statements)

References 59 publications

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“…GSEA analysis revealed that B3GNT3 might contribute to the chemokine-mediated activity of the PI3K signaling pathway, and indicated the negative correlation between B3GNT3 expression and immunostimulator expression. CCL2 is required for tumor-associated macrophages to induce immune evasion ( 26 ), to promote cancer cell progression ( 27 ) and invasion ( 28 ). Furthermore, CCL4 is associated with a T cell-inflamed phenotype in primary and metastatic pancreatic cancer ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

B3GNT3: A prognostic biomarker associated with immune cell infiltration in pancreatic adenocarcinoma

et al. 2020

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Pancreatic cancer, one of the most malignant gastrointestinal tumors, is prone to liver metastasis. However, due to the lack of appropriate and comprehensive diagnostic methods, it is difficult to accurately predict the survival outcomes. Therefore, there is a need to identify effective biomarkers, such as UDP-GlcNAc: βGal β-1,3-N-acetylglucosaminyltransferase 3 ( B3GNT3 ), that predict the survival outcome of patients with pancreatic cancer. In the present study, based on data from 171 cases of pancreatic cancer obtained from The Cancer Genome Atlas portal, the differential expression of mRNAs was screened by comparing cancerous tissues with adjacent tissues. Univariate Cox regression analysis demonstrated that B3GNT3 had prognostic capability and could be an independent prognostic factor for pancreatic adenocarcinoma (PAAD). Using the Tumor Immune Estimation Resource tool and Tumor-Immune System Interaction Database, a potential relationship between B3GNT3 expression and immune cell infiltration was identified in pancreatic carcinoma. Furthermore, 177 samples of pancreatic carcinoma were collected and the association of CD68 expression with B3GNT3 was assessed by immunohistochemical staining. B3GNT3 expression was associated with clinical outcomes in pancreatic carcinoma and related to infiltrating levels of immune cells, which indicated that B3GNT3 could be used as an immunotherapy target for PAAD.

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Section: Discussionmentioning

confidence: 99%

B3GNT3: A prognostic biomarker associated with immune cell infiltration in pancreatic adenocarcinoma

et al. 2020

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“…In addition, the CCL2-CCR2 signaling pathway regulates macrophage polarization during cancer treatment. In a mouse model of non-small-cell lung cancer (NSCLC), it has been shown that estrogen receptor alpha (Erα) can activate the CCL2-CCR2 axis to promote macrophage infiltration, M2 polarization and MMP9 production, which increased NSCLC cell invasion [ 83 ]. Mechanistically, ERα was shown to bind to estrogen response elements on the CCL2 promoter, thereby increasing CCL2 expression.…”

Section: Macrophages In Tumor Therapymentioning

confidence: 99%

“…Mechanistically, ERα was shown to bind to estrogen response elements on the CCL2 promoter, thereby increasing CCL2 expression. Using anti-estrogens or CCR2 antagonists to target the CCL2-CCR2 axis may improve outcomes in NSCLC [ 83 ]. In a murine breast tumor model, targeting the CCL2-CCR2 axis by complexes of CCR2 siRNAs and TAT cell penetrating peptides enhanced the efficacy of immunotherapy and promoted the reprogramming of TAMs [ 84 ].…”

Section: Macrophages In Tumor Therapymentioning

confidence: 99%

Functionalized Nanoparticles Targeting Tumor-Associated Macrophages as Cancer Therapy

Júnior

Cruz

et al. 2021

Pharmaceutics

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The tumor microenvironment (TME) plays a central role in regulating antitumor immune responses. As an important part of the TME, alternatively activated type 2 (M2) macrophages drive the development of primary and secondary tumors by promoting tumor cell proliferation, tumor angiogenesis, extracellular matrix remodeling and overall immunosuppression. Immunotherapy approaches targeting tumor-associated macrophages (TAMs) in order to reduce the immunosuppressive state in the TME have received great attention. Although these methods hold great potential for the treatment of several cancers, they also face some limitations, such as the fast degradation rate of drugs and drug-induced cytotoxicity of organs and tissues. Nanomedicine formulations that prevent TAM signaling and recruitment to the TME or deplete M2 TAMs to reduce tumor growth and metastasis represent encouraging novel strategies in cancer therapy. They allow the specific delivery of antitumor drugs to the tumor area, thereby reducing side effects associated with systemic application. In this review, we give an overview of TAM biology and the current state of nanomedicines that target M2 macrophages in the course of cancer immunotherapy, with a specific focus on nanoparticles (NPs). We summarize how different types of NPs target M2 TAMs, and how the physicochemical properties of NPs (size, shape, charge and targeting ligands) influence NP uptake by TAMs in vitro and in vivo in the TME. Furthermore, we provide a comparative analysis of passive and active NP-based TAM-targeting strategies and discuss their therapeutic potential.

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“…On the other hand, the expression of ER is related to the secretion of chemokines, which acts as the bridge between cancer cells and immune cells. The estrogen and ERα expression enhances the secretion of CCL2 and increases the expression level of macrophage-induced C-X-C Motif Chemokine Ligand 12 (CXCL12) [ 125 , 126 ]. Meanwhile, ERα can also promote the CXCL11 secretion of cancer cells and activate EMT induced by CXCR7 [ 127 ].…”

Section: Cytokines and Chemokinesmentioning

confidence: 99%

Estrogen/ER in anti-tumor immunity regulation to tumor cell and tumor microenvironment

Wang¹,

Jin

Qian

et al. 2021

Cancer Cell Int

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As the essential sexual hormone, estrogen and its receptor has been proved to participate in the regulation of autoimmunity diseases and anti-tumor immunity. The adjustment of tumor immunity is related to the interaction between cancer cells, immune cells and tumor microenvironment, all of which is considered as the potential target in estrogen-induced immune system regulation. However, the specific mechanism of estrogen-induced immunity is poorly understood. Typically, estrogen causes the nuclear localization of estrogen/estrogen receptor complex and alternates the transcription pattern of target genes, leading to the reprogramming of tumor cells and differentiation of immune cells. However, the estrogen-induced non-canonical signal pathway activation is also crucial to the rapid function of estrogen, such as NF-κB, MAPK-ERK, and β-catenin pathway activation, which has not been totally illuminated. So, the investigation of estrogen modulatory mechanisms in these two manners is vital for the tumor immunity and can provide the potential for endocrine hormone targeted cancer immunotherapy. Here, this review summarized the estrogen-induced canonical and non-canonical signal transduction pathway and aimed to focus on the relationship among estrogen and cancer immunity as well as immune-related tumor microenvironment regulation. Results from these preclinical researches elucidated that the estrogen-target therapy has the application prospect of cancer immunotherapy, which requires the further translational research of these treatment strategies.

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Estrogen receptor α promotes lung cancer cell invasion via increase of and cross‐talk with infiltrated macrophages through the CCL2/CCR2/MMP9 and CXCL12/CXCR4 signaling pathways

Cited by 35 publications

References 59 publications

B3GNT3: A prognostic biomarker associated with immune cell infiltration in pancreatic adenocarcinoma

B3GNT3: A prognostic biomarker associated with immune cell infiltration in pancreatic adenocarcinoma

Functionalized Nanoparticles Targeting Tumor-Associated Macrophages as Cancer Therapy

Estrogen/ER in anti-tumor immunity regulation to tumor cell and tumor microenvironment

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