Expression of the CXCL12/CXCR4 chemokine axis predicts regional control in head and neck squamous cell carcinoma

León, Xavier; Diez, Santiago; García, José María Sánchez; Lop, Joan; Sumarroca, Anna; Quer, Miquel; Camacho, Mercedes

doi:10.1007/s00405-016-4144-9

Cited by 15 publications

(10 citation statements)

References 37 publications

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“…Leon et al. ( 53 ) also found that low CXCL12 expression levels are significantly related to a high-risk of recurrence of HNSCC. In our study, no abnormal expression of CXCL12 was found in HNSCC tissues.…”

Section: Discussionmentioning

confidence: 95%

Analysis of the Prognosis and Therapeutic Value of the CXC Chemokine Family in Head and Neck Squamous Cell Carcinoma

Gong

et al. 2021

Front. Oncol.

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The CXC chemokines belong to a family which includes 17 different CXC members. Accumulating evidence suggests that CXC chemokines regulate tumor cell proliferation, invasion, and metastasis in various types of cancers by influencing the tumor microenvironment. The different expression profiles and specific function of each CXC chemokine in head and neck squamous cell carcinoma (HNSCC) are not yet clarified. In our work, we analyzed the altered expression, interaction network, and clinical data of CXC chemokines in patients with HNSCC by using the following: the Oncomine dataset, cBioPortal, Metascape, String analysis, GEPIA, and the Kaplan–Meier plotter. The transcriptional level analysis suggested that the mRNA levels of CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, CXCL9, CXCL10, CXCL11, and CXCL13 increased in HNSCC tissue samples when compared to the control tissue samples. The expression levels of CXCL9, CXCL10, CXCL11, CXCL12, and CXCL14 were associated with various tumor stages in HNSCC. Clinical data analysis showed that high transcription levels of CXCL2, CXCL3, and CXCL12, were linked with low relapse-free survival (RFS) in HNSCC patients. On the other hand, high CXCL14 levels predicted high RFS outcomes in HNSCC patients. Meanwhile, increased gene transcription levels of CXCL9, CXCL10, CXCL13, CXCL14, and CXCL17 were associated with a higher overall survival (OS) advantage in HNSCC patients, while high levels of CXCL1, and CXCL8 were associated with poor OS in all HNSCC patients. This study implied that CXCL1, CXCL2, CXCL3, CXCL8, and CXCL12 could be used as prognosis markers to identify low survival rate subgroups of patients with HNSCC as well as be potential suitable therapeutic targets for HNSCC patients. Additionally, CXCL9, CXCL10, CXCL13, CXCL14, and CXCL17 could be used as functional prognosis biomarkers to identify better survival rate subgroups of patients with HNSCC.

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Section: Discussionmentioning

confidence: 95%

Analysis of the Prognosis and Therapeutic Value of the CXC Chemokine Family in Head and Neck Squamous Cell Carcinoma

Gong

et al. 2021

Front. Oncol.

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“…In our study SDF-1 was on average lower in p16 positive tumours and no association between CXCR4 expression and p16 could be found. A more complex prognostic pattern for SDF-1 and CXCR4 is suggested from a study on 111 HNSCC patients who were treated with surgery, surgery plus postoperative RT/RT-CT or with primary RT/RT-CT [58] . In addition, Clatot and colleagues [59] found that lower SDF-1 expression determined by PCR in tumour specimen of 71 HNSCC patients was correlating with worse disease-free survival and cancer specific survival.…”

Section: Discussionmentioning

confidence: 99%

SDF-1/CXCR4 expression in head and neck cancer and outcome after postoperative radiochemotherapy

De-Colle

Mönnich

Welz

et al. 2017

Clinical and Translational Radiation Oncology

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“…In this context, targeting the chemokine receptor 4 (CXCR4) has emerged as a promising approach in cancer treatment. CXCR4 overexpression in HNSCC primary tumors associates with a higher risk of developing loco-regional recurrences and distant metastases after treatment and worse overall survival [ 7 , 8 ]. Moreover, preclinical and clinical data suggest that this chemokine pathway contributes to a resistant phenotype [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

CXCR4-targeted nanotoxins induce GSDME-dependent pyroptosis in head and neck squamous cell carcinoma

Rioja-Blanco

Arroyo‐Solera

Álamo

et al. 2022

J Exp Clin Cancer Res

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Background Therapy resistance, which leads to the development of loco-regional relapses and distant metastases after treatment, constitutes one of the major problems that head and neck squamous cell carcinoma (HNSCC) patients currently face. Thus, novel therapeutic strategies are urgently needed. Targeted drug delivery to the chemokine receptor 4 (CXCR4) represents a promising approach for HNSCC management. In this context, we have developed the self-assembling protein nanotoxins T22-PE24-H6 and T22-DITOX-H6, which incorporate the de-immunized catalytic domain of Pseudomonas aeruginosa (PE24) exotoxin A and the diphtheria exotoxin (DITOX) domain, respectively. Both nanotoxins contain the T22 peptide ligand to specifically target CXCR4-overexpressing HNSCC cells. In this study, we evaluate the potential use of T22-PE24-H6 and T22-DITOX-H6 nanotoxins for the treatment of HNSCC. Methods T22-PE24-H6 and T22-DITOX-H6 CXCR4-dependent cytotoxic effect was evaluated in vitro in two different HNSCC cell lines. Both nanotoxins cell death mechanisms were assessed in HNSCC cell lines by phase-contrast microscopy, AnnexinV/ propidium iodide (PI) staining, lactate dehydrogenase (LDH) release assays, and western blotting. Nanotoxins antitumor effect in vivo was studied in a CXCR4+ HNSCC subcutaneous mouse model. Immunohistochemistry, histopathology, and toxicity analyses were used to evaluate both nanotoxins antitumor effect and possible treatment toxicity. GSMDE and CXCR4 expression in HNSCC patient tumor samples was also assessed by immunohistochemical staining. Results First, we found that both nanotoxins exhibit a potent CXCR4-dependent cytotoxic effect in vitro. Importantly, nanotoxin treatment triggered caspase-3/Gasdermin E (GSDME)-mediated pyroptosis. The activation of this alternative cell death pathway that differs from traditional apoptosis, becomes a promising strategy to bypass therapy resistance. In addition, T22-PE24-H6 and T22-DITOX-H6 displayed a potent antitumor effect in the absence of systemic toxicity in a CXCR4+ subcutaneous HNSCC mouse model. Lastly, GSDME was found to be overexpressed in tumor tissue from HNSCC patients, highlighting the relevance of this strategy. Conclusions Altogether, our results show that T22-PE24-H6 and T22-DITOX-H6 represent a promising therapy for HNSCC patients. Remarkably, this is the first study showing that both nanotoxins are capable of activating caspase-3/GSDME-dependent pyroptosis, opening a novel avenue for HNSCC treatment.

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Expression of the CXCL12/CXCR4 chemokine axis predicts regional control in head and neck squamous cell carcinoma

Cited by 15 publications

References 37 publications

Analysis of the Prognosis and Therapeutic Value of the CXC Chemokine Family in Head and Neck Squamous Cell Carcinoma

Analysis of the Prognosis and Therapeutic Value of the CXC Chemokine Family in Head and Neck Squamous Cell Carcinoma

SDF-1/CXCR4 expression in head and neck cancer and outcome after postoperative radiochemotherapy

CXCR4-targeted nanotoxins induce GSDME-dependent pyroptosis in head and neck squamous cell carcinoma

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