High expression of C-C chemokine receptor 2 associates with poor overall survival in gastric cancer patients after surgical resection

Li, Ruochen; Zhang, Heng; Líu, Hao; Lin, Chao; Cao, Yifan; Zhang, Weijuan; Shen, Zhongliang; Xu, Jiejie

doi:10.18632/oncotarget.8069

Cited by 9 publications

(4 citation statements)

References 42 publications

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“…Thus, CCR2‐positive cells infiltrations were shown not in the stomach but rather in the small intestine. Previous study and our study have also reported that CCR2‐positive cells were seldom seen in gastric tissues but were present in gastric cancer tissues . Since central injection of Ucn 2 affects on gastrointestinal tract through activating the sympathetic nervous system, inhibition of the vagus nerve may worsen intestinal mucosal inflammation.…”

Section: Discussionsupporting

confidence: 61%

Acotiamide attenuates central urocortin 2‐induced intestinal inflammatory responses, and urocortin 2 treatment reduces TNF‐α productions in LPS‐stimulated macrophage cell lines

Yanagawa

Futagami

Sakasegawa

et al. 2020

Neurogastroenterology Motil

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Background To determine whether central and in vitro administration of urocortin 2 (Ucn 2) affected intestinal inflammatory responses in LPS‐stimulated rat models and macrophage cell lines and acotiamide modified mucosal inflammation in this model. Methods Rats were divided into four groups. LPS‐stimulated group (n = 4); LPS‐ and urocortin 2‐treated group (n = 4); LPS‐ and acotiamide‐treated group (n = 4); and LPS‐, urocortin 2‐, and acotiamide‐treated group (n = 4). CD68‐, CCR2‐, and corticotropin‐releasing hormone receptor type 2 (CRHR2)‐positive cells were assessed by immunostaining. Myeloperoxidase (MPO) activity was measured. TNF‐α, IL‐6, and IL‐4 levels were measured by ELISA method. Gastric emptying and small intestinal transit time were determined using Evans blue. Key Results Central administration of Ucn 2 significantly aggravated infiltrations of CD68‐ and CCR2‐positive cells in the intestinal mucosa of LPS‐stimulated rat models compared to those in LPS treatment alone. Interestingly, acotiamide treatment significantly reduced the migrations of both CD68‐ and CCR2‐positive cells in the jejunum of central Ucn 2‐treated LPS‐stimulated rat models. Acotiamide significantly reduced the expression levels of IkB‐α phosphorylation in LPS‐ and MCP‐1‐stimulated NR8383 cells. Central administration of Ucn 2 significantly delayed gastric emptying. In contrast, Ucn 2 stimulation significantly reduced TNF‐α and IL‐6 productions in LPS‐stimulated NR8383 cells and astressin B reversed the inhibition of TNF‐α production in stimulated NR8383 cells. Acotiamide (30 μmol/L) significantly reduced TNF‐α and IL‐6 productions in LPS‐ and MCP‐1‐stimulated NR8383 cells. Conclusions and Inferences Central and in vitro treatments of Ucn 2 affected intestinal inflammatory responses, respectively, and acotiamide improved them.

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Section: Discussionsupporting

confidence: 61%

Acotiamide attenuates central urocortin 2‐induced intestinal inflammatory responses, and urocortin 2 treatment reduces TNF‐α productions in LPS‐stimulated macrophage cell lines

Yanagawa

Futagami

Sakasegawa

et al. 2020

Neurogastroenterology Motil

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“…The efficacy of CCL2‐CCR2 axis inhibition has been widely investigated in numerous preclinical experiments. CCL2 and CCR2 can function as diagnostic biomarkers, 164 and are correlated with the prognosis and poor overall survival in cancer patients 105,165 . Given the critical roles of the CCL2‐CCR2 signalling axis in tumorigenesis, a series of clinical trials targeting this axis have been launched continually (Table 2).…”

Section: Ccl2‐ccr2‐associated Targeted Therapymentioning

confidence: 99%

Role of the CCL2‐CCR2 signalling axis in cancer: Mechanisms and therapeutic targeting

et al. 2021

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The chemokine ligand CCL2 and its receptor CCR2 are implicated in the initiation and progression of various cancers. CCL2 can activate tumour cell growth and proliferation through a variety of mechanisms. By interacting with CCR2, CCL2 promotes cancer cell migration and recruits immunosuppressive cells to the tumour microenvironment, favouring cancer development. Over the last several decades, a series of studies have been conducted to explore the CCL2‐CCR2 signalling axis function in malignancies. Therapeutic strategies targeting the CCL2‐ CCR2 axis have also shown promising effects, enriching our approaches for fighting against cancer. In this review, we summarize the role of the CCL2‐CCR2 signalling axis in tumorigenesis and highlight recent studies on CCL2‐CCR2 targeted therapy, focusing on preclinical studies and clinical trials.

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“…CCL2 has been suggested as a potential biomarker for several types of cancer, including prostate [ 105 , 106 , 107 , 108 ]. Given the critical roles of the CCL2-CCR2 signaling axis in tumorigenesis, a series of clinical trials targeting this axis have been carried out in several cancers [ 102 , 107 ].…”

Section: Targeting Macrophages In Cancer Therapy and Its Application In Pcmentioning

confidence: 99%

Macrophages as a Therapeutic Target in Metastatic Prostate Cancer: A Way to Overcome Immunotherapy Resistance?

Martori

Sanchez‐Moral

Paul

et al. 2022

Cancers

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Prostate cancer (PC) is the most common malignancy and the fifth cause of cancer death in men. The treatment for localized or locally advanced stages offers a high probability of cure. Even though the therapeutic landscape has significantly improved over the last decade, metastatic PC (mPC) still has a poor prognosis mainly due to the development of therapy resistance. In this context, the use of immunotherapy alone or in combination with other drugs has been explored in recent years. However, T-cell directed immune checkpoint inhibitors (ICIs) have shown limited activity with inconclusive results in mPC patients, most likely due to the highly immunosuppressive PC tumor microenvironment (TME). In this scenario, targeting macrophages, a highly abundant immunosuppressive cell type in the TME, could offer a new therapeutic strategy to improve immunotherapy efficacy. In this review, we summarize the growing field of macrophage-directed immunotherapies and discuss how these could be applied in the treatment of mPC, focusing on their combination with ICIs.

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High expression of C-C chemokine receptor 2 associates with poor overall survival in gastric cancer patients after surgical resection

Cited by 9 publications

References 42 publications

Acotiamide attenuates central urocortin 2‐induced intestinal inflammatory responses, and urocortin 2 treatment reduces TNF‐α productions in LPS‐stimulated macrophage cell lines

Acotiamide attenuates central urocortin 2‐induced intestinal inflammatory responses, and urocortin 2 treatment reduces TNF‐α productions in LPS‐stimulated macrophage cell lines

Role of the CCL2‐CCR2 signalling axis in cancer: Mechanisms and therapeutic targeting

Macrophages as a Therapeutic Target in Metastatic Prostate Cancer: A Way to Overcome Immunotherapy Resistance?

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