The Association Between Elevated EphB4 Expression, Smoking Status, and Advanced-Stage Disease in Patients With Head and Neck Squamous Cell Carcinoma

Sinha, Uttam K.; Mazhar, Kashif; Chinn, Steven B.; Dhillon, Vaninder K.; Lihua, Liu; Masood, Rizwan; Rice, Dale H.; Gill, Parkash S.

doi:10.1001/archotol.132.10.1053

Cited by 19 publications

(22 citation statements)

References 21 publications

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“…The expression trend described here for HNSCC is in close agreement with reports by Masood et al (Masood et al, 2006), which found that tumor expression of EPHB4 in HNSCC increased with disease stage (in primary tumor tissues and nodal metastases), by Sinha et al (Sinha et al, 2006), which reported that EPHB4 expression correlated both with stage of HNSCC as well as with progression from normal status to cancer, and by Yavrouian et al (Yavrouian et al, 2008), which demonstrated that increased EPHB4 expression in HNSCC is correlated with shorter survival. However, no previous studies have investigated the expression of EPHB4 in pre-HNSCC dysplastic tissue; to our knowledge, these data are the first to address the expression pattern of a kinase in paired head and neck tissues with progression from normal status through dysplasia to cancer and therefore shed significant light on the role of EPHB4 in HNSCC progression.…”

Section: Discussionsupporting

confidence: 93%

Expression of the EPHB4 receptor tyrosine kinase in head and neck and renal malignancies – implications for solid tumors and potential for therapeutic inhibition

Ferguson¹,

Tretiakova²,

Lingen³

et al. 2014

Growth Factors

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Solid malignancies are often characterized by overexpression of various receptor tyrosine kinases (RTKs) against which many targeted therapies are currently in use and in active development. EPHB4 has recently emerged as a frequently overexpressed RTK in many types of cancer. Here, we demonstrate expression patterns of EPHB4 in two solid malignancies, squamous cell carcinoma of the head and neck (HNSCC) and renal cell carcinoma (RCC), by immunohistochemical analysis. We demonstrate the first association between EPHB4 expression and progression of HNSCC from normal tissue to dysplasia and to cancer. Interestingly, most RCC subtypes exhibited expression patterns that were opposite from that found in HNSCC, possibly owing to their unique biology and high degree of organ and tumor vasculature. Taken together, these results suggest a possible role for EPHB4 as a therapeutic target in these malignancies.

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Section: Discussionsupporting

confidence: 93%

Expression of the EPHB4 receptor tyrosine kinase in head and neck and renal malignancies – implications for solid tumors and potential for therapeutic inhibition

Ferguson¹,

Tretiakova²,

Lingen³

et al. 2014

Growth Factors

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“…EphB4 is similarly over-expressed in head and neck cancers (100% of 37 cases examined) and knockout studies using siRNA and antisense both in vitro and importantly, in vivo , have demonstrated that EphB4 has an essential role in many processes that contribute to cancer cell survival and spread [16,17]. Cytokeratins such as CK19 are almost exclusively expressed in epithelial tissues and are commonly used as markers for the detection of disseminated tumour cells of epithelial origin [18-20].…”

Section: Introductionmentioning

confidence: 99%

Long term survival following the detection of circulating tumour cells in head and neck squamous cell carcinoma

et al. 2009

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BackgroundTechniques for detecting circulating tumor cells in the peripheral blood of patients with head and neck cancers may identify individuals likely to benefit from early systemic treatment.MethodsReconstruction experiments were used to optimise immunomagnetic enrichment and RT-PCR detection of circulating tumor cells using four markers (ELF3, CK19, EGFR and EphB4). This method was then tested in a pilot study using samples from 16 patients with advanced head and neck carcinomas.ResultsSeven patients were positive for circulating tumour cells both prior to and after surgery, 4 patients were positive prior to but not after surgery, 3 patients were positive after but not prior to surgery and 2 patients were negative. Two patients tested positive for circulating cells but there was no other evidence of tumor spread. Given this patient cohort had mostly advanced disease, as expected the detection of circulating tumour cells was not associated with significant differences in overall or disease free survival.ConclusionFor the first time, we show that almost all patients with advanced head and neck cancers have circulating cells at the time of surgery. The clinical application of techniques for detection of spreading disease, such as the immunomagnetic enrichment RT-PCR analysis used in this study, should be explored further.

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“…Of note, EphB4 expression is limited in normal adult tissue12, which makes it an ideal target for therapeutic intervention. Previous studies have reported an association between EphB4 overexpression and advancement of disease13. Winter et al .…”

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confidence: 97%

Enhancing radiosensitization in EphB4 receptor-expressing Head and Neck Squamous Cell Carcinomas

Sharma

Oweida

Griego

et al. 2016

Sci Rep

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Members of the Eph family of receptor tyrosine kinases have been implicated in a wide array of human cancers. The EphB4 receptor is ubiquitously expressed in head and neck squamous cell carcinoma (HNSCC) and has been shown to impart tumorigenic and invasive characteristics to these cancers. In this study, we investigated whether EphB4 receptor targeting can enhance the radiosensitization of HNSCC. Our data show that EphB4 is expressed at high to moderate levels in HNSCC cell lines and patient-derived xenograft (PDX) tumors. We observed decreased survival fractions in HNSCC cells following EphB4 knockdown in clonogenic assays. An enhanced G2 cell cycle arrest with activation of DNA damage response pathway and increased apoptosis was evident in HNSCC cells following combined EphB4 downregulation and radiation compared to EphB4 knockdown and radiation alone. Data using HNSCC PDX models showed significant reduction in tumor volume and enhanced delay in tumor regrowth following sEphB4-HSA administration with radiation compared to single agent treatment. sEphB4-HSA is a protein known to block the interaction between the EphB4 receptor and its ephrin-B2 ligand. Overall, our findings emphasize the therapeutic relevance of EphB4 targeting as a radiosensitizer that can be exploited for the treatment of human head and neck carcinomas.

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The Association Between Elevated EphB4 Expression, Smoking Status, and Advanced-Stage Disease in Patients With Head and Neck Squamous Cell Carcinoma

Abstract: To examine the expression of EphB4 in tumor tissue, surrounding normal tissue, and metastatic lymph node in patients with head and neck squamous cell carcinoma (HNSCC) and to evaluate its association with disease stage and smoking.

Cited by 19 publications

References 21 publications

Expression of the EPHB4 receptor tyrosine kinase in head and neck and renal malignancies – implications for solid tumors and potential for therapeutic inhibition

Expression of the EPHB4 receptor tyrosine kinase in head and neck and renal malignancies – implications for solid tumors and potential for therapeutic inhibition

Long term survival following the detection of circulating tumour cells in head and neck squamous cell carcinoma

Enhancing radiosensitization in EphB4 receptor-expressing Head and Neck Squamous Cell Carcinomas

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