Intracellular expression profile and clinical significance of the CCR9–CCL25 chemokine receptor complex in nasopharyngeal carcinoma

Lf, Ye; Huang, Jingyu; Lp, Zhang; Chen, Z

doi:10.1017/s0022215115002108

Cited by 7 publications

(7 citation statements)

References 30 publications

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“…In conclusion, disruption of the CCR9/ CCL25 axis in tumor bearers may affect homeostasis of the common lymphoid system and compromise the delicate balance between gut and systemic immunity (45). Nonetheless, several observations point to a cellautonomous role of CCR9/CCL25 in cancer cell migration, invasion, and metastatic dissemination as well as in PI3Kdependent resistance to chemotherapy (46)(47)(48)(49)(50)(51). Enforced CCR9 expression on colorectal cancer cells dictated their niching in mouse intestines after xenografting, whereas CCL25 blockade enhanced liver metastases (52).…”

Section: Discussionmentioning

confidence: 99%

Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma

Jacquelot¹,

Enot²,

Flament³

et al. 2016

Journal of Clinical Investigation

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Melanoma prognosis is dictated by tumor-infiltrating lymphocytes, the migratory and functional behavior of which is guided by chemokine or cytokine gradients. Here, we retrospectively analyzed the expression patterns of 9 homing receptors (CCR/CXCR) in naive and memory CD4+ and CD8+ T lymphocytes in 57 patients with metastatic melanoma (MMel) with various sites of metastases to evaluate whether T cell CCR/CXCR expression correlates with intratumoral accumulation, metastatic progression, and/or overall survival (OS). Homing receptor expression on lymphocytes strongly correlated with MMel dissemination. Loss of CCR6 or CXCR3, but not cutaneous lymphocyte antigen (CLA), on circulating T cell subsets was associated with skin or lymph node metastases, loss of CXCR4, CXCR5, and CCR9 corresponded with lung involvement, and a rise in CCR10 or CD103 was associated with widespread dissemination. High frequencies of CD8+CCR9+ naive T cells correlated with prolonged OS, while neutralizing the CCR9/CCL25 axis in mice stimulated tumor progression. The expansion of CLA-expressing effector memory CD8+ T cells in response to a single administration of CTLA4 blockade predicted disease control at 3 months in 47 patients with MMel. Thus, specific CCR/CXCR expression patterns on circulating T lymphocytes may guide potential diagnostic and therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma

Jacquelot¹,

Enot²,

Flament³

et al. 2016

Journal of Clinical Investigation

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“…More and more studies have indicated that CCR9 could be viewed as an oncogenic biomarker in predicting metastasis and prognosis for cancer patients. Increased expression of CCR9 and CCL25 have been identified in various tumors, such as nasopharyngeal carcinoma and ovarian cancer [9,31]. Upregulated expression of CCR9 and CCL25 were correlated with advanced tumor stage and poor overall survival [9,31].…”

Section: Discussionmentioning

confidence: 99%

CCR9 Promotes Migration and Invasion of Lung Adenocarcinoma Cancer Stem Cells

Lü¹,

Du²,

Huang³

et al. 2020

Int. J. Med. Sci.

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Aim: CC chemokine receptor 9 (CCR9) interacts with its exclusive ligand CCL25, resulting in promoting tumor progression and metastasis. However, the effect and mechanisms of CCR9 on lung adenocarcinoma distant metastasis remain largely unknown. To preliminary clarify the underlying mechanisms, we investigate the correlation between CCR9 and ALDH1A1 + cancer stem cells (CSCs), as well as the effect of CCR9 on the migration and invasion of CSCs. Methods: Immunohistochemistry was performed to detect the expression of CCR9 in lung adenocarcinoma tissues. The correlations of CCR9 with distant metastasis and overall survival were investigated. Serial paraffin-embedded tissue blocks were used to detect ALDH1A1 + CSCs expression. The correlations between CCR9 expression and ALDH1A1 + CSCs were evaluated. We further studied the effect of CCR9/CCL25 on the migration and invasion of CSCs using transwell assays. Results: There were positive correlations between CCR9 expression and distant metastasis, as well as poor overall survival. Patients with high CCR9 expression were more likely to develop distant metastasis and demonstrated poorer overall survival than patients with low CCR9 expression. In addition, there was positive correlation between the expression of CCR9 and ALDH1A1 in the same tumor microenvironment. ALDH high CSCs demonstrated enhanced expression of CCR9 than ALDH low cells. Further transwell assays demonstrated that the numbers of CSCs migrated or invaded in response to CCL25 were more than that without CCL25 stimulation. Additional application of anti-CCR9 antibody reversed the CCL25-induced migration and invasion of CSCs. Conclusions:In summary, our study demonstrated that CCR9/CCL25 promoted the migration and invasion of CSCs, which might contribute to distant metastasis and poor overall survival. Our findings provided evidence that CCR9/CCL25 could be used as novel therapeutic targets for lung adenocarcinoma.

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“…Of note, CCL25 and its specific receptor CCR9 play an important role in the proliferation and chemotaxis of inflammatory cells (Qiuping et al, 2004). Currently, research regarding CCR9/CCL25 is mostly concentrated in the fields of rheumatoid arthritis (Yokoyama et al, 2014), inflammatory bowel disease (Igaki et al, 2018), hepatitis (Nakamoto et al, 2012) and tumors (Ye, Huang, Zhang, & Chen, 2015). To better understand the role of CCR9/CCL25 in cancer, we highlight recent advances and provide a thorough evaluation of the CCR9/CCL25 mechanism of action in different types of cancer.…”

Section: Structure and Function Of Ccr9 And Ccl25mentioning

confidence: 99%

“…In addition, CCL25 facilitated the proliferation of nasopharyngeal carcinoma CNE‐2 cells in a concentration‐dependent manner. Knocking down CCR9 suppressed the CCL25‐induced proliferation of CNE‐2 cells, also in a concentration‐dependent manner (Ye et al, 2015). Clearly, CCR9/CCL25 is a powerful antiproliferative agent of cancer cells.…”

Section: Cellular Functions Of Ccr9/ccl25 In Cancer Cellsmentioning

confidence: 99%

“…However, the intestine‐prone metastasis of CCR9 + tumor cells is probably because CCL25 is preferentially expressed in the intestine (and thymus), and may also explain why CCR9 + colon tumor cells are less metastatic (H. J. Chen et al, 2012). In nasopharyngeal carcinoma, the upregulation of CCR9 and CCL25 is correlated with the tumor‐node‐metastasis (TNM) stage (Ye et al, 2015). Notably, the regulation of melanoma cell metastasis by the CCR9/CCL25 signaling pathway is debated.…”

Section: Cellular Functions Of Ccr9/ccl25 In Cancer Cellsmentioning

confidence: 99%

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CCR9 and CCL25: A review of their roles in tumor promotion

Deng

et al. 2020

Journal Cellular Physiology

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Chemokines constitute a superfamily of small chemotactic cytokines with functions that are based on interactions with their corresponding receptors. It has been found that, among other functions, chemokines regulate the migratory and invasive abilities of cancer cells. Multiple studies have confirmed that chemokine receptor 9 (CCR9) and its exclusive ligand, chemokine 25 (CCL25), are overexpressed in a variety of malignant tumors and are closely associated with tumor proliferation, apoptosis, invasion, migration and drug resistance. This review evaluates recent advances in understanding the role of CCR9/CCL25 in cancer development. First, we outline the general background of chemokines in cancer and the structure and function of CCR9 and CCL25. Next, we describe the basic function of CCR9/CCL25 in the cancer process. Then, we introduce the role of CCR9/CCL25 and related signaling pathways in various cancers. Finally, future research directions are proposed. In general, this paper is intended to serve as a comprehensive repository of information on this topic and is expected to contribute to the design of other research projects and future efforts to develop treatment strategies for ameliorating the effects of CCR9/CCL25 in cancer.

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Intracellular expression profile and clinical significance of the CCR9–CCL25 chemokine receptor complex in nasopharyngeal carcinoma

Abstract: The extent of CCR9 and CCL25 upregulation in nasopharyngeal carcinoma correlates with the tumour-node-metastasis stage.

Cited by 7 publications

References 30 publications

Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma

Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma

CCR9 Promotes Migration and Invasion of Lung Adenocarcinoma Cancer Stem Cells

CCR9 and CCL25: A review of their roles in tumor promotion

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