Tumor-associated macrophages promote lung metastasis and induce epithelial-mesenchymal transition in osteosarcoma by activating the COX-2/STAT3 axis

Han, Yu; W, Guo; Ren, Tingting; Huang, Yi; Wang, Shidong; Liu, Kuisheng; Zheng, Bingxin; Kang, Yang; Zhang, Hongliang; Liang, Xin

doi:10.1016/j.canlet.2018.10.011

Cited by 141 publications

(116 citation statements)

References 52 publications

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“…In addition, IL-6 secreted by macrophages can up-regulate COX-2 expression and PGE2 secretion in lung cancer cells, and then COX-2 and PGE2 further promote lung cancer cell metastasis by inducing EMT through b-catenin transposition from the cytoplasm to nucleus (102), which indicates that the high expression of COX-2 in TAMs can also up-regulate the COX-2 in tumor cells through the secretion of IL-6 to promote the process of tumor metastasis. Indeed, TAMs have been proven to promote tumor cell migration and invasion by up-regulating COX-2 and MMP9 expression in osteosarcoma (OS) cells, promoting phosphorylation of STAT3 and inducing epithelialmesenchymal transformation (EMT) (103). Trigger receptor (TREM)-1, a member of the hyperimmunoglobulin family, is primarily expressed in monocytes/macrophages and is highly expressed in colon, liver, and lung cancer tissues.…”

Section: Tumors Utilize Tams To Promote Metastasismentioning

confidence: 99%

The Crosstalk Between Tumor-Associated Macrophages (TAMs) and Tumor Cells and the Corresponding Targeted Therapy

2020

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Tumor microenvironment (TME) is composed of tumor cells and surrounding non-tumor stromal cells, mainly including tumor associated macrophages (TAMs), endothelial cells, and carcinoma-associated fibroblasts (CAFs). The TAMs are the major components of non-tumor stromal cells, and play an important role in promoting the occurrence and development of tumors. Macrophages originate from bone marrow hematopoietic stem cells and embryonic yolk sacs. There is close crosstalk between TAMs and tumor cells. With the occurrence of tumors, tumor cells secrete various chemokines to recruit monocytes to infiltrate tumor tissues and further promote their M2-type polarization. Importantly, M2-like TAMs can in turn accelerate tumor growth, promote tumor cell invasion and metastasis, and inhibit immune killing to promote tumor progression. Therefore, targeting TAMs in tumor tissues has become one of the principal strategies in current tumor immunotherapy. Current treatment strategies focus on reducing macrophage infiltration in tumor tissues and reprogramming TAMs to M1like to kill tumors. Although these treatments have had some success, their effects are still limited. This paper mainly summarized the recruitment and polarization of macrophages by tumors, the support of TAMs for the growth of tumors, and the research progress of TAMs targeting tumors, to provide new treatment strategies for tumor immunotherapy.

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Section: Tumors Utilize Tams To Promote Metastasismentioning

confidence: 99%

The Crosstalk Between Tumor-Associated Macrophages (TAMs) and Tumor Cells and the Corresponding Targeted Therapy

2020

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“…Apparently, the observed level of COX-2 expression might be affected by the number of acromegaly and prolactinoma participants in the current study, which should be refined by further studies. Interestingly, the up-regulation of COX-2 was accompanied by STAT3 phosphorylation and facilitation of epithelial-mesenchymal transition (EMT), which resulted in osteosarcoma metastasis and invasion [33]. Moreover, inhibition of COX-2 caused attenuated migration and invasion of radiation-resistant lung cancer cells through the involvement of specificity protein 1 (Sp1) [34].…”

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase enzyme and PGE2 expression in patients with functional and non-functional pituitary adenomas

et al. 2020

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Background: Pituitary adenomas as multifactorial intracranial neoplasms impose a massive burden of morbidity on patients and characterizing the molecular mechanism underlying their pathogenesis has received considerable attention. Despite the appealing role of cyclooxygenase enzymes and their bioactive lipid products in cancer pathogenesis, their relevance to pituitary adenoma pathogenesis is debated and yet to be determined. Thus, the current study perused this relevance. Methods: The expression level of the isoforms of cyclooxygenase (COX-1 and COX-2) was evaluated in hormonesecreting and inactive pituitary adenoma tumors and normal pituitary tissues through Real-Time PCR. The level of PGE2, as the main product of enzymes, was assessed using enzyme immunoassay kits in patients and healthy subjects. Results: The results of the current study demonstrated that COX-1 and COX-2 expression levels were increased in pituitary tumors including non-functional pituitary adenoma (NFPA), acromegaly, Cushing's disease and prolactinoma compared with normal pituitary tissues. A significant expression level of COX-2 was observed in NFPA compared with the other pituitary tumors. Furthermore, the COX-2 expression level was significantly increased in macroadenoma and invasive tumors. The level of PGE2 was consistent with COX enzymes enhanced in pituitary adenoma tumors compared with healthy pituitary tissue. A significant elevation in the PGE2 level was detected in NFPA compared with hormone-secreting pituitary tumors. Additionally, the PGE2 level was increased in macroadenoma compared with microadenoma and in invasive compared with non-invasive pituitary tumors. The diagnostic values of cyclooxygenase isoforms and PGE2 were considerable between patients and healthy groups; however, COX-2 revealed more value in distinguishing endocrinologically active and non-active pituitary tumors. Conclusions: Data from the current study provides expression patterns of COX-1, COX-2 and PGE2 in prevalent pituitary tumors and their association with patients' clinical features which may open up new molecular targets for early diagnosis/follow up of pituitary tumor growth.

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“…This result can be veri ed in both TCGA and CGGA databases. Previous studies have shown a clear relationship between JAK-STAT signaling pathways, EMT and drug resistance [50], while TAMS can induce the occurrence of EMT [21], and studies in other tumors have found CD276,HAVCR2 and CD163 associated with AKT signaling pathways and EMT [51][52][53], but little is known about the relationship in GBM. To explore upstream regulatory factors that may affect CD276/HAVCR2 high expression in GBM.…”

Section: Discussionmentioning

confidence: 99%

“…Epithelial-mesenchymal transition (EMT) plays an important role in tumor invasion, metastasis and so on, and is closely related to its related inducers, transcription factors, signaling pathway genes and tumorassociated macrophages (TAMS), and TAMS can induce EMT [21,22]. Most of the immune cells in brain tumors are macrophages.…”

Section: Introductionmentioning

confidence: 99%

The High Expression of CD276/HAVCR2 and CD163 is an Adverse Immune Subtype of Glioblastoma and is Closely Related to Epithelial-Mesenchymal Transition

Hou

Zhou

Fan

et al. 2020

Preprint

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Background Glioblastoma (GBM) is one of the most malignant tumors that can afflict the central nervous system. Previous studies have observed that there are individual differences in the treatment response of immune checkpoint inhibitors in glioblastoma. This study’s aim is to ascertain the factors that may affect the efficacy of immunosuppressant therapy. Methods The clinical data of this study were obtained from a public database. Then, the data was analyzed and processed by R software and corresponding R package. To verify the results of the analysis, information was gathered from 89 GBM patients in our hospital and thereafter the corresponding paraffin sections were stained and quantitatively analyzed by immunohistochemistry. Results From the analysis, it was observed that both CD276 and HAVCR2 were significantly overexpressed in GBM and could be associated with patient prognosis. The analysis of single cell RNA sequencing data and GBM data analysis found an immune subtype with poor prognosis. Further analysis found that the high expression of CD276, HAVCR2 and CD163 was closely related to epithelial-mesenchymal transition (EMT) and could affect the patient prognosis of PD-L1 high expression. GSVA enrichment analysis showed that CD276, HAVCR2 and CD163 might induce EMT by JAK-STAT3 signaling pathway, and RUNX1 and IKZF1 might be transcription factors that regulate CD276/HAVCR2 high expression. Conclusions We found an immune subtype with poor prognosis of GBM, the high expression of CD276, HAVCR2 and CD163 with EMT are closely related and may be one of the factors affecting the efficacy of Anti-PD-L1.

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Tumor-associated macrophages promote lung metastasis and induce epithelial-mesenchymal transition in osteosarcoma by activating the COX-2/STAT3 axis

Cited by 141 publications

References 52 publications

The Crosstalk Between Tumor-Associated Macrophages (TAMs) and Tumor Cells and the Corresponding Targeted Therapy

The Crosstalk Between Tumor-Associated Macrophages (TAMs) and Tumor Cells and the Corresponding Targeted Therapy

Cyclooxygenase enzyme and PGE2 expression in patients with functional and non-functional pituitary adenomas

The High Expression of CD276/HAVCR2 and CD163 is an Adverse Immune Subtype of Glioblastoma and is Closely Related to Epithelial-Mesenchymal Transition

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