Chemokines and chemokine receptors: A new strategy for breast cancer therapy

Liu, Hui; Yang, Zhenjiang; Lü, Wenping; Chen, Zhe; Chen, Lianyu; Han, Shuyu; Wu, Xiaoyu; Cai, Tiange; Cai, Yu

doi:10.1002/cam4.3014

Cited by 82 publications

(70 citation statements)

References 101 publications

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“…The primary role of chemokines is to participate in leukocyte development, differentiation, and migration. However, chemokines are also involved in angiogenesis, wound healing, inflammatory diseases, and progression of malignancies, such as adult T-cell leukemia and many solid tumors [ 6 , 7 , 8 , 9 , 10 ]. Although chemokines exert antitumor effects, including induction of cytotoxic T cells into tumor tissues, they have also been known to assist cells that suppress tumor immunity, such as tumor-associated macrophages (TAM), myeloid-derived immune suppressor cells (MDSC), and regulatory T cells (Treg) [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

The CCL20-CCR6 Axis in Cancer Progression

Kadomoto

Izumi

Mizokami

2020

IJMS

164

111

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Chemokines, which are basic proteins that exert their effects via G protein-coupled receptors and a subset of the cytokine family, are mediators deeply involved in leukocyte migration during an inflammatory reaction. Chemokine (C-C motif) ligand 20 (CCL20), also known as macrophage inflammatory protein (MIP)-3α, liver activation regulated chemokine (LARC), and Exodus-1, is a small protein that is physiologically expressed in the liver, colon, and skin, is involved in tissue inflammation and homeostasis, and has a specific receptor C-C chemokine receptor 6 (CCR6). The CCL20-CCR6 axis has long been known to be involved in inflammatory and infectious diseases, such as rheumatoid arthritis and human immunodeficiency virus infections. Recently, however, reports have shown that the CCL20-CCR6 axis is associated with several cancers, including hepatocellular carcinoma, colorectal cancer, breast cancer, pancreatic cancer, cervical cancer, and kidney cancer. The CCL20-CCR6 axis promotes cancer progression directly by enhancing migration and proliferation of cancer cells and indirectly by remodeling the tumor microenvironment through immune cell control. The present article reviewed the role of the CCL20-CCR6 axis in cancer progression and its potential as a therapeutic target.

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Section: Introductionmentioning

confidence: 99%

The CCL20-CCR6 Axis in Cancer Progression

Kadomoto

Izumi

Mizokami

2020

IJMS

164

111

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“…Chemokines and chemokine receptors play crucial roles in the progression of breast cancer, including its occurrence, immune responses, angiogenesis, metastasis, and drug resistance [ 2 ]. Our study aimed to evaluate the roles of XCL1 and its specific receptor XCR1 in MDA-MB-231 cell migration as well as to identify the underlying signaling pathway mediating this process.…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, the effectiveness of current pharmacological therapies for breast cancer is generally limited. Thus, developing new strategies to effectively reduce breast cancer progression and metastasis is crucial [ 2 ]. Novel immunotherapies targeting the chemokine system, including chemokines and their receptors, are promising strategies for breast cancer therapy [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…Thus, developing new strategies to effectively reduce breast cancer progression and metastasis is crucial [ 2 ]. Novel immunotherapies targeting the chemokine system, including chemokines and their receptors, are promising strategies for breast cancer therapy [ 2 ]. Therefore, current research has focused on elucidating the roles of the chemokine system in breast cancer metastasis.…”

Section: Introductionmentioning

confidence: 99%

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Involvement of the ERK/HIF-1α/EMT Pathway in XCL1-Induced Migration of MDA-MB-231 and SK-BR-3 Breast Cancer Cells

Thu

Cho

2020

IJMS

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Chemokine–receptor interactions play multiple roles in cancer progression. It was reported that the overexpression of X-C motif chemokine receptor 1 (XCR1), a specific receptor for chemokine X-C motif chemokine ligand 1 (XCL1), stimulates the migration of MDA-MB-231 triple-negative breast cancer cells. However, the exact mechanisms of this process remain to be elucidated. Our study found that XCL1 treatment markedly enhanced MDA-MB-231 cell migration. Additionally, XCL1 treatment enhanced epithelial–mesenchymal transition (EMT) of MDA-MB-231 cells via E-cadherin downregulation and upregulation of N-cadherin and vimentin as well as increases in β-catenin nucleus translocation. Furthermore, XCL1 enhanced the expression of hypoxia-inducible factor-1α (HIF-1α) and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Notably, the effects of XCL1 on cell migration and intracellular signaling were negated by knockdown of XCR1 using siRNA, confirming XCR1-mediated actions. Treating MDA-MB-231 cells with U0126, a specific mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, blocked XCL1-induced HIF-1α accumulation and cell migration. The effect of XCL1 on cell migration was also evaluated in ER-/HER2+ SK-BR-3 cells. XCL1 also promoted cell migration, EMT induction, HIF-1α accumulation, and ERK phosphorylation in SK-BR-3 cells. While XCL1 did not exhibit any significant impact on the matrix metalloproteinase (MMP)-2 and -9 expressions in MDA-MB-231 cells, it increased the expression of these enzymes in SK-BR-3 cells. Collectively, our results demonstrate that activation of the ERK/HIF-1α/EMT pathway is involved in the XCL1-induced migration of both MDA-MB-231 and SK-BR-3 breast cancer cells. Based on our findings, the XCL1–XCR1 interaction and its associated signaling molecules may serve as specific targets for the prevention of breast cancer cell migration and metastasis.

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“…Furthermore, the good tumor marker should be highly sensitive, easy to measure, and reproducible. A large number of observations suggested that intrinsic properties of the tumor cells, as well as macro-environmental factors, with a direct interaction of the tumor cells with chemokines and their receptors, are involved in breast tumorigenesis and tumor progression (Liu et al, 2020;Suman et al, 2016). Chemokines and chemokine receptors play a crucial role in these processes since they participate in the trafficking of cells into and out of the tumor microenvironment (Ali & Lazennec, 2007).…”

Section: Introductionmentioning

confidence: 99%

C-C motif chemokine ligand 5 and C-C chemokine receptor type 5: possible diagnostic application in breast cancer patients

et al. 2020

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The chemokine CCL5 and its receptor CCR5 play important roles in cancer invasion and metastasis. Based on our knowledge, our results were the first that presented the diagnostic usefulness of CCL5 and CCR5 in breast cancer (BC) patients, based on receiver operating characteristic (ROC) curve analysis. We wished to examine further if CCL5 and CCR5 are appropriate to be applied as BC markers for early screening. Values of tested parameters in patients’ plasma were determined by CMIA method (Chemiluminescent Microparticle Immunoassay, CA 15-3) as well as by ELISA method (Enzyme-Linked Immunosorbent Assay, CCL5 and CCR5). Levels of CCL5 in the plasma were markedly increased, while those of CCR5 were remarkably lower in BC patients when compared to the control groups. Moreover, higher levels of CCL5 in BC corresponded to advanced tumor stage, while the levels of CCR5 decreased with increasing the disease stage. CCL5 concentration was characterized by high sensitivity (SE) (68.04%) and high specificity (SP) (100.00%) in the BC patients. Results indicated that area under the curve (AUC) corresponding to CCL5 (0.8116) had a higher value than this corresponding to CA 15-3. The AUC value of CCL5 was significantly increased in the early phase of BC (stage I – 0.7089; stage II – 0.8313). The maximum range in the BC patients was observed for the combined analysis of the tested measurands with CA 15-3 (0.8335). In conclusion, our research indicates that examination of plasma CCL5 and CCR5 may be useful in BC diagnosis at the early stage of the disorder, especially when combined with CA 15-3.

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Chemokines and chemokine receptors: A new strategy for breast cancer therapy

Cited by 82 publications

References 101 publications

The CCL20-CCR6 Axis in Cancer Progression

The CCL20-CCR6 Axis in Cancer Progression

Involvement of the ERK/HIF-1α/EMT Pathway in XCL1-Induced Migration of MDA-MB-231 and SK-BR-3 Breast Cancer Cells

C-C motif chemokine ligand 5 and C-C chemokine receptor type 5: possible diagnostic application in breast cancer patients

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