CXCL12 expression promotes esophageal squamous cell carcinoma proliferation and worsens the prognosis

Uchi, Yusuke; Takeuchi, Hiroya; Matsuda, Sachiko; Saikawa, Yoshiro; Kawakubo, Hirofumi; Wada, Norihito; Takahashi, Tsunehiro; Nakamura, Rieko; Fukuda, Kazumasa; Omori, Tai; Kitagawa, Yuko

doi:10.1186/s12885-016-2555-z

Cited by 19 publications

(12 citation statements)

References 31 publications

(24 reference statements)

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“…Overexpression of CXCR4 has been implicated in tumour metastasis and has been found to metastasise to tissues with a high concentration of CXCL12, such as lungs, liver and bone marrow (Balkwill, ). Interestingly, immunohistochemistry on 79 oesophageal squamous cell carcinoma tissue samples found that the proliferation index was higher in patients samples with higher expression of CXCR4 or CXCL12 (Uchi et al ., ). This effect on cell proliferation was also observed in vitro where inhibition of CXCR4 suppressed proliferation of synovial sarcoma cell lines (Kimura et al ., ).…”

Section: Discussionmentioning

confidence: 97%

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: 97%

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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“…Recent reports evaluating biopsy samples of esophageal cancer tumors demonstrated a high intensity of CXCR4 receptor expression [26,27]. Additionally, chemokine receptor expression was a predictor of poor recurrence-free and overall survival [28][29][30][31].…”

Section: Discussionmentioning

confidence: 99%

Pentixafor PET/CT for imaging of chemokine receptor 4 expression in esophageal cancer – a first clinical approach

et al. 2021

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Background Expression of CXCR4, a chemokine (C-X-C motif) receptor that plays a central role in tumor growth and metastasis of circulating tumor cells, has been described in a variety of solid tumors. A high expression of CXCR4 has a prognostic significance with regard to overall and progression-free survival and offers a starting point for targeted therapies. In this context, [68]Ga-Pentixafor-Positron Emission Tomography/Computer Tomography (PET/CT) offers promising possibility of imaging the CXCR4 expression profile. We set out to compare a [18F] fluorodeoxyglucose (FDG)-PET/CT and a [68Ga]Pentixafor-PET/CT in (re-)staging and radiation planning of patients with localized esophageal cancer. Materials and methods In this retrospective analysis, ten patients, with adeno- or squamous cell carcinoma of the esophagus (n = 3 and n = 7, respectively), which were scheduled for radio (chemo) therapy, were imaged using both Pentixafor and FDG PET/CT examinations. All lesions were visually rated as Pentixafor and FDG positive or negative. For both tracers, SUVmax was measured all lesions and compared to background. Additionally, immunohistochemistry of CXCR4 was obtained in patients undergoing surgery. Results FDG-positive tumor-suspicious lesions were detected in all patients and a total of 26 lesions were counted. The lesion-based analysis brought equal status in 14 lesions which were positive for both tracers while five lesions were FDG positive and Pentixafor negative and seven lesions were FDG negative, but Pentixafor positive. Histopathologic correlation was available in seven patients. The CXCR4 expression of four non-pretreated tumour lesion samples was confirmed immunohistochemically. Conclusion Our data shows that additional PET/CT imaging with Pentixafor for imaging the CXCR4 chemokine receptor is feasible but heterogeneous in both newly diagnosed and pretreated recurrent esophageal cancer. In addition, the Pentixafor PET/CT may serve as complementary tool for radiation field expansion in radiooncology.

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“…Moreover, CXCR4 plays a key role in the self-renewal of CSCs in drug-resistant NSCLC [201]. Due to the powerful protumor activities of CXCL12/CXCR4 axis, numerous studies have consistently shown that their expression is associated with poor prognosis for patients in esophageal cancer [202], acute myelogenous leukemia [203], BC [204,205], HCC [206], and NSCLC [207]. In addition, CXCR4 expression correlates with the degree of tumor infiltration and promotes a more aggressive phenotype in papillary thyroid carcinoma [208], and is also a negative prognostic marker for response to chemotherapy in NHL [209].…”

Section: Cxcl12/cxcr4mentioning

confidence: 99%

Chemokines and their Receptors: Multifaceted Roles in Cancer Progression and Potential Value as Cancer Prognostic Markers

Thu

Lee

Cho

2020

Cancers

157

131

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Chemokines are chemotactic cytokines that mediate immune cell chemotaxis and lymphoid tissue development. Recent advances have indicated that chemokines and their cognate receptors play critical roles in cancer-related inflammation and cancer progression. On the basis of these findings, the chemokine system has become a new potential drug target for cancer immunotherapy. In this review, we summarize the essential roles of the complex network of chemokines and their receptors in cancer progression. Furthermore, we discuss the potential value of the chemokine system as a cancer prognostic marker. The chemokine system regulates the infiltration of immune cells into the tumor microenvironment, which induces both pro- and anti-immunity and promotes or suppresses tumor growth and proliferation, angiogenesis, and metastasis. Increasing evidence indicates the promising prognostic value of the chemokine system in cancer patients. While CCL2, CXCL10, and CX3CL1/CX3CR1 can serve as favorable or unfavorable prognostic factors depending on the cancer types, CCL14 and XCL1 possess good prognostic value. Other chemokines such as CXCL1, CXCL8, and CXCL12 are poor prognostic markers. Despite vast advances in our understanding of the complex nature of the chemokine system in tumor biology, knowledge about the multifaceted roles of the chemokine system in different types of cancers is still limited. Further studies are necessary to decipher distinct roles within the chemokine system in terms of cancer progression and to validate their potential value in cancer prognosis.

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CXCL12 expression promotes esophageal squamous cell carcinoma proliferation and worsens the prognosis

Cited by 19 publications

References 31 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

Pentixafor PET/CT for imaging of chemokine receptor 4 expression in esophageal cancer – a first clinical approach

Chemokines and their Receptors: Multifaceted Roles in Cancer Progression and Potential Value as Cancer Prognostic Markers

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