GATA3 as a master regulator for interactions of tumor-associated macrophages with high-grade serous ovarian carcinoma

El‐Arabey, Amr Ahmed; Denizli, Merve; Kanlikilicer, Pınar; Bayraktar, Recep; Ivan, Cristina; Rashed, Mohammed H.; Kabil, Nashwa; Özpolat, Bülent; Calin, George A.; Salama, Salama Abdou; Abd-Allah, Adel R. A.; Sood, Anil K.; López-Berestein, Gabriel

doi:10.1016/j.cellsig.2020.109539

Cited by 97 publications

(59 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Preclinical and clinical data show a close relationship between high infiltration of TAMs and a poor prognosis in most types of tumors (4), such as pancreatic ductal adenocarcinoma (PDAC) (5), glioblastoma (6), and bladder cancer (7). On the other hand, TAM infiltration has also been found to be associated with a favorable prognosis in some cases, such as in ovarian cancer (8) and colorectal cancer (9). Such different outcomes can be attributed to not only the distinct cancer types but also some intra-tumoral factors, such as the TAM distribution in the TME.…”

Section: Introductionmentioning

confidence: 99%

Redefining Tumor-Associated Macrophage Subpopulations and Functions in the Tumor Microenvironment

et al. 2020

View full text Add to dashboard Cite

The immunosuppressive status of the tumor microenvironment (TME) remains poorly defined due to a lack of understanding regarding the function of tumor-associated macrophages (TAMs), which are abundant in the TME. TAMs are crucial drivers of tumor progression, metastasis, and resistance to therapy. Intra-and inter-tumoral spatial heterogeneities are potential keys to understanding the relationships between subpopulations of TAMs and their functions. Antitumor M1-like and pro-tumor M2-like TAMs coexist within tumors, and the opposing effects of these M1/M2 subpopulations on tumors directly impact current strategies to improve antitumor immune responses. Recent studies have found significant differences among monocytes or macrophages from distinct tumors, and other investigations have explored the existence of diverse TAM subsets at the molecular level. In this review, we discuss emerging evidence highlighting the redefinition of TAM subpopulations and functions in the TME and the possibility of separating macrophage subsets with distinct functions into antitumor M1-like and pro-tumor M2-like TAMs during the development of tumors. Such redefinition may relate to the differential cellular origin and monocyte and macrophage plasticity or heterogeneity of TAMs, which all potentially impact macrophage biomarkers and our understanding of how the phenotypes of TAMs are dictated by their ontogeny, activation status, and localization. Therefore, the detailed landscape of TAMs must be deciphered with the integration of new technologies, such as multiplexed immunohistochemistry (mIHC), mass cytometry by time-of-flight (CyTOF), single-cell RNA-seq (scRNA-seq), spatial transcriptomics, and systems biology approaches, for analyses of the TME.

show abstract

Section: Introductionmentioning

confidence: 99%

Redefining Tumor-Associated Macrophage Subpopulations and Functions in the Tumor Microenvironment

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In addition, GATA3 has also been proved to promote the differentiation of T cells into Th2 cells by increasing cell effector Th2, thus affecting the immune response of tumor cells [38]. Likewise, GATA3 also promoted the proliferation and invasion of high-serous ovarian cancer cells by regulating M2-type macrophage polarization [39]. Similar results were observed in our study, GATA3, worked as a downstream target of GNAS-AS1/miR-433-3p axis, was identified to promote the M2 polarization of macrophages and enhance the capabilities of proliferation, migration and invasion of ER + breast cancer cells.…”

mentioning

confidence: 99%

LncRNA GNAS-AS1 facilitates ER+ breast cancer cells progression by promoting M2 macrophage polarization via regulating miR-433-3p/GATA3 axis

et al. 2020

View full text Add to dashboard Cite

Objective: ER+ breast cancer is the most common type of breast cancer, which seriously affects the physical and mental health of women. Recently, lncRNAs mediated tumor-associated macrophages (TAM) were identified to involve in tumorigenesis. Therefore, the present study aimed at demonstrating the regulatory network of GNAS-AS1 in TAM-mediated ER+ breast cancer progress. Methods: The expression levels of genes were evaluated using qRT-PCR. The proportions of polarized macrophages (M1, M2) were assessed by flow cytometry. Cell proliferation, migration and invasion were evaluated by CCK-8, wound healing and transwell assay, respectively. Double-luciferase reporter system was used to detect the interaction between molecules. Western blot was applied to test protein levels. Results: The expression of GNAS-AS1 was obviously increased in ER+ breast cancer tissues and cell lines, as well as M2 macrophages. GNAS-AS1 facilitated the capabilities of proliferation, migration and invasion of ER+ breast cancer cells by accelerating M2 macrophage polarization via directly sponging miR-433-3p. GATA3, as a target of miR-433-3p, could positively regulate by GNAS-AS1. Furthermore, either miR-433-3p overexpression or GATA3 knockdown impaired the effects of GNAS-AS1 on M2 macrophage polarization and ER+ breast cancer cells progression. Conclusion: GNAS-AS1/miR-433-3p/GATA3 axis promoted proliferation, metastasis of ER+ breast cancer cells by accelerating M2 macrophage polarization. The mechanism may provide a new strategy and target for ER+ breast cancer treatment.

show abstract

“…Moreover, it was observed that lactic acid produced by cancer cells promotes tumor growth via enriching M2-like macrophages as well as enhancing vascular endothelial growth factor (VEGF) expression [ 32 ]. TAMs increase the ovarian cancer tumor growth via secreting developmental transcription factors including GATA binding protein-3 (GATA-3) through exosomes [ 33 ].…”

Section: Diverse Strategies Opted By Tams To Promote Tumor Progresmentioning

confidence: 99%

MicroRNAs: As Critical Regulators of Tumor- Associated Macrophages

Chatterjee

Saha

Bose

et al. 2020

IJMS

View full text Add to dashboard Cite

Emerging shreds of evidence suggest that tumor-associated macrophages (TAMs) modulate various hallmarks of cancer during tumor progression. Tumor microenvironment (TME) prime TAMs to execute important roles in cancer development and progression, including angiogenesis, matrix metalloproteinases (MMPs) secretion, and extracellular matrix (ECM) disruption. MicroRNAs (miRNAs) are critical epigenetic regulators, which modulate various functions in diverse types of cells, including macrophages associated with TME. In this review article, we provide an update on miRNAs regulating differentiation, maturation, activation, polarization, and recruitment of macrophages in the TME. Furthermore, extracellular miRNAs are secreted from cancerous cells, which control macrophages phenotypic plasticity to support tumor growth. In return, TAMs also secrete various miRNAs that regulate tumor growth. Herein, we also describe the recent updates on the molecular connection between tumor cells and macrophages. A better understanding of the interaction between miRNAs and TAMs will provide new pharmacological targets to combat cancer.

show abstract

GATA3 as a master regulator for interactions of tumor-associated macrophages with high-grade serous ovarian carcinoma

Cited by 97 publications

References 57 publications

Redefining Tumor-Associated Macrophage Subpopulations and Functions in the Tumor Microenvironment

Redefining Tumor-Associated Macrophage Subpopulations and Functions in the Tumor Microenvironment

LncRNA GNAS-AS1 facilitates ER+ breast cancer cells progression by promoting M2 macrophage polarization via regulating miR-433-3p/GATA3 axis

MicroRNAs: As Critical Regulators of Tumor- Associated Macrophages

Contact Info

Product

Resources

About