CXCR4 antagonist inhibits perineural invasion of adenoid cystic carcinoma

Jeong, Woo Jin; Choi, Ik Joon; Park, Min Woo; An, Soo Youn; Jeon, Eun Hui; Paik, Jin Ho; Sung, Myung Whun; Ahn, Sang‐Hyeon

doi:10.1136/jclinpath-2014-202349

Cited by 15 publications

(11 citation statements)

References 28 publications

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“…). CXCR4 has been heavily linked to an increasingly invasive phenotype in a variety of cancers types; however, many of the studies have looked at CXCR4 invasion in only a 2D setting (Guo et al ., ; Jeong et al ., ; Niu et al ., ; Xu et al ., ; Ying et al ., ). To our knowledge, this is the first experimental evidence of miR‐9 knockdown inducing an invasive phenotype via CXCR4 in 3D culture.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐9 inhibits growth and invasion of head and neck cancer cells and is a predictive biomarker of response to plerixafor, an inhibitor of its target CXCR4

et al. 2018

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Head and neck squamous cell carcinomas (HNSCC) are associated with poor morbidity and mortality. Current treatment strategies are highly toxic and do not benefit over 50% of patients. There is therefore a crucial need for predictive and/or prognostic biomarkers to allow treatment stratification for individual patients. One class of biomarkers that has recently gained importance are microRNA (miRNA). MiRNA are small, noncoding molecules which regulate gene expression post‐transcriptionally. We performed miRNA expression profiling of a cohort of head and neck tumours with known clinical outcomes. The results showed miR‐9 to be significantly downregulated in patients with poor treatment outcome, indicating its role as a potential biomarker in HNSCC. Overexpression of miR‐9 in HNSCC cell lines significantly decreased cellular proliferation and inhibited colony formation in soft agar. Conversely, miR‐9 knockdown significantly increased both these features. Importantly, endogenous CXCR4 expression levels, a known target of miR‐9, inversely correlated with miR‐9 expression in a panel of HNSCC cell lines tested. Induced overexpression of CXCR4 in low expressing cells increased proliferation, colony formation and cell cycle progression. Moreover, CXCR4‐specific ligand, CXCL12, enhanced cellular proliferation, migration, colony formation and invasion in CXCR4‐overexpressing and similarly in miR‐9 knockdown cells. CXCR4‐specific inhibitor plerixafor abrogated the oncogenic phenotype of CXCR4 overexpression as well as miR‐9 knockdown. Our data demonstrate a clear role for miR‐9 as a tumour suppressor microRNA in HNSCC, and its role seems to be mediated through CXCR4 suppression. MiR‐9 knockdown, similar to CXCR4 overexpression, significantly promoted aggressive HNSCC tumour cell characteristics. Our results suggest CXCR4‐specific inhibitor plerixafor as a potential therapeutic agent, and miR‐9 as a possible predictive biomarker of treatment response in HNSCC.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‐9 inhibits growth and invasion of head and neck cancer cells and is a predictive biomarker of response to plerixafor, an inhibitor of its target CXCR4

et al. 2018

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“…The association between CXCR4 and PNI has also been noted in pancreatic cancer (Jiang, Li, Sun, Zhao, & Zhou, 2014). Lastly, Jeong et al showed that CXCR4 was expressed in the regions surrounding the areas of PNI in adenoid cystic carcinoma samples (Jeong et al, 2014). In the same study, it was reported that administering AMD31000 in a murine PNI model reduced the incidence of PNI from 71.4% to 18.8%.…”

Section: Other Potential Players: Ncam and Cxcr4mentioning

confidence: 79%

“…Of note, in each of these trials it not possible to determine whether the observed effect was due to inhibition of RET or alternatively Flk-1 (the VEGF receptor) as SU5416 targets both. Lastly, as previously mentioned, AMD3100 (plerixafor) a CXCR4 inhibitor, has been shown inhibit PNI in mouse models of adenoid cystic carcinoma (Jeong et al, 2014). Plerixafor is better known for its use in mobilizing hematopoietic stem cells into the peripheral circulation in cancer patients (Uy, Rettig, & Cashen, 2008) although CXCR4's potential association with poor prognosis in melanomas suggests targeting this receptor may be worth investigating in melanomas.…”

Section: Clinical Potential Of Neurotrophins As Therapeutic Targetsmentioning

confidence: 96%

Neurotrophin Receptors and Perineural Invasion

Frydenlund

Mahalingam²

2017

Vitamins and Hormones

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“…Also, AMD3100 has the anti-angiogenic efficacy that is associated with a reduction of tumor growth and invasiveness in orthotopic glioblastoma xenotransplanted rats (Ali et al, 2013). In another study, the clinical relevance of CXCR4 neutralization with siRNA or AMD3100 in chondrosarcoma and adenoid cystic carcinoma (ACC) were investigated and the results indicated a decreased tumor growth and metastasis dissemination (Jeong et al, 2014). AMD3100 is used as a cell mobilizing drug in stem cell therapy and also has an anti-HIV potential for AIDS patients (De Clercq, 2015).…”

Section: Amd3100mentioning

confidence: 99%

CXCR4 and CCR7: Two eligible targets in targeted cancer therapy

Mishan

Ahmadiankia

Bahrami

2016

Cell Biology International

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Cancer is one of the most common cause of death in the world with high negative emotional, economic, and social impacts. Conventional therapeutic methods, including chemotherapy and radiotherapy, have not proven satisfactory and relapse is common in most cases. Recent studies have focused on targeted therapy with more precise identification and targeted attacks to the cancer cells. For this purpose, chemokine receptors are proper targets and among them, CXCR4 and CCR7, with a crucial role in cancer metastasis, are being considered as desired candidates for investigation. In this review paper, the most important experimental results are highlighted on the potential targeted therapies based on CXCR4 and CCR7 chemokine receptors.

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CXCR4 antagonist inhibits perineural invasion of adenoid cystic carcinoma

Abstract: CXCR4 is associated with perineural invasion in ACC. AMD3100, which can effectively diminish perineural invasion of ACC, may have an adjuvant role in the management of ACC.

Cited by 15 publications

References 28 publications

MicroRNA‐9 inhibits growth and invasion of head and neck cancer cells and is a predictive biomarker of response to plerixafor, an inhibitor of its target CXCR4

MicroRNA‐9 inhibits growth and invasion of head and neck cancer cells and is a predictive biomarker of response to plerixafor, an inhibitor of its target CXCR4

Neurotrophin Receptors and Perineural Invasion

CXCR4 and CCR7: Two eligible targets in targeted cancer therapy

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