C-C motif chemokine receptor 1 (CCR1) is a target of the EGF-AKT-mTOR-STAT3 signaling axis in breast cancer cells

Shin, Soon Young; Lee, Da Hyun; Lee, Ji-Shin; Choi, Chan; Kim, Jiyoung; Nam, Jeong‐Seok; Lim, Yoongho; Lee, Young Han

doi:10.18632/oncotarget.21813

Cited by 29 publications

(22 citation statements)

References 44 publications

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“…52–57 CCR1 and its ligand CCL5 have been associated with cancer cell invasion and metastasis. 58–60 Similar observations have been reported for the CCR2-CCL2, CCR5-CCL2,3,4,5, CCR7-CCL19,21 and CCR8-CCL18 axes. 61–69 The role of FPR1 in tumor progression remains controversial as it has been associated with tumor invasion in colorectal cancer but with tumor suppression in gastric cancer.…”

Section: Resultssupporting

confidence: 81%

Impact of chemotactic factors and receptors on the cancer immune infiltrate: a bioinformatics study revealing homogeneity and heterogeneity among patient cohorts

et al. 2018

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Multiple soluble factors including proteins (in particular chemokines), non-proteinaceous factors released by dead cells, as well as receptors for such factors (in particular chemokine receptors, formyl peptide receptors and purinergic receptors), influence the recruitment of distinct cell subsets into the tumor microenvironment. We performed an extensive bioinformatic analysis on tumor specimens from 5953 cancer patients to correlate the mRNA expression levels of chemotactic factors/receptors with the density of immune cell types infiltrating the malignant lesions. This meta-analysis, which included specimens from breast, colorectal, lung, ovary and head and neck carcinomas as well as melanomas, revealed that a subset of chemotactic factors/receptors exhibited a positive and reproducible correlation with several infiltrating cell types across various solid cancers, revealing a universal pattern of association. Hence, this meta-analysis distinguishes between homogeneous associations that occur across different cancer types and heterogeneous correlations, that are specific of one organ. Importantly, in four out of five breast cancer cohorts for which clinical data were available, the levels of expression of chemotactic factors/receptors that exhibited universal (rather than organ-specific) positive correlations with the immune infiltrate had a positive impact on the response to neoadjuvant chemotherapy. These results support the notion that general (rather than organ-specific) rules governing the recruitment of immune cells into the tumor bed are particularly important in determining local immunosurveillance and response to therapy.

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Section: Resultssupporting

confidence: 81%

Impact of chemotactic factors and receptors on the cancer immune infiltrate: a bioinformatics study revealing homogeneity and heterogeneity among patient cohorts

et al. 2018

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“…In a separate study, CCR1 sustained liver metastasis by promoting local recruitment of bone marrow (BM)-derived cells that secrete the MMP9 and MMP2 metalloproteinases required for tissue invasion 45 . Activation of EGFR signaling via CCR1 has been shown to contribute to breast cancer invasion and metastasis 46 . The CCR1 mediated interaction between macrophages and breast cancer cells induced a chemokine cascade that enhanced metastasis 19 .…”

Section: Discussionmentioning

confidence: 99%

Omental macrophages secrete chemokine ligands that promote ovarian cancer colonization of the omentum via CCR1

Krishnan¹,

Tallapragada²,

Schaar

et al. 2020

Commun Biol

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The omentum is the most common site of ovarian cancer metastasis. Immune cell clusters called milky spots are found throughout the omentum. It is however unknown if these immune cells contribute to ovarian cancer metastasis. Here we report that omental macrophages promote the migration and colonization of ovarian cancer cells to the omentum through the secretion of chemokine ligands that interact with chemokine receptor 1 (CCR1). We found that depletion of macrophages reduces ovarian cancer colonization of the omentum. RNA-sequencing of macrophages isolated from mouse omentum and mesenteric adipose tissue revealed a specific enrichment of chemokine ligand CCL6 in omental macrophages. CCL6 and the human homolog CCL23 were both necessary and sufficient to promote ovarian cancer migration by activating ERK1/2 and PI3K pathways. Importantly, inhibition of CCR1 reduced ovarian cancer colonization. These findings demonstrate a critical mechanism of omental macrophage induced colonization by ovarian cancer cells via CCR1 signaling.

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“…19,21 . CCR1 seems to be a very important receptor because it is a target of several chemokines [CC motif chemokine ligand 2 (CCL2), CCL3, CCL4, CCL5, CCL6, CCL7 and CCL9], 4,[23][24][25][26][27] which have been suggested to be involved in the pathogenesis of neuropathic pain. [28][29][30] There is some evidence demonstrating that CCR1 is involved in nociception.…”

Section: Introductionmentioning

confidence: 99%

The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

et al. 2020

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Summary A growing body of evidence has indicated that the release of nociceptive factors, such as interleukins and chemokines, by activated immune and glial cells has crucial significance for neuropathic pain generation and maintenance. Moreover, changes in the production of nociceptive immune factors are associated with low opioid efficacy in the treatment of neuropathy. Recently, it has been suggested that CC chemokine receptor type 1 (CCR1) signaling is important for nociception. Our study provides evidence that the development of hypersensitivity in rats following chronic constriction injury (CCI) of the sciatic nerve is associated with significant up‐regulation of endogenous CCR1 ligands, namely, CCL2, CCL3, CCL4, CCL6, CCL7 and CCL9 in the spinal cord and CCL2, CCL6, CCL7 and CCL9 in dorsal root ganglia (DRG). We showed that single and repeated intrathecal administration of J113863 (an antagonist of CCR1) attenuated mechanical and thermal hypersensitivity. Moreover, repeated administration of a CCR1 antagonist enhanced the analgesic properties of morphine and buprenorphine after CCI. Simultaneously, repeated administration of J113863 reduced the protein levels of IBA‐1 in the spinal cord and MPO and CD4 in the DRG and, as a consequence, the level of pronociceptive factors, such as interleukin‐1β (IL‐1β), IL‐6 and IL‐18. The data obtained provide evidence that CCR1 blockade reduces hypersensitivity and increases opioid‐induced analgesia through the modulation of neuroimmune interactions.

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C-C motif chemokine receptor 1 (CCR1) is a target of the EGF-AKT-mTOR-STAT3 signaling axis in breast cancer cells

Cited by 29 publications

References 44 publications

Impact of chemotactic factors and receptors on the cancer immune infiltrate: a bioinformatics study revealing homogeneity and heterogeneity among patient cohorts

Impact of chemotactic factors and receptors on the cancer immune infiltrate: a bioinformatics study revealing homogeneity and heterogeneity among patient cohorts

Omental macrophages secrete chemokine ligands that promote ovarian cancer colonization of the omentum via CCR1

The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

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