EphB4 provides survival advantage to squamous cell carcinoma of the head and neck |
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Authors: | Masood Rizwan Kumar S Ram Sinha Uttam K Crowe David L Krasnoperov Valery Reddy Ramachandra K Zozulya Sergey Singh Jasbir Xia Guangbin Broek Daniel Schönthal Axel H Gill Parkash S |
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Institution: | Department of Pathology, University of Southern California, Los Angeles, CA 90033, USA. |
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Abstract: | The receptor tyrosine kinase EphB4 and its ligand EphrinB2 play critical roles in blood vessel maturation, and are frequently overexpressed in a wide variety of cancers. We studied the aberrant expression and biological role of EphB4 in head and neck squamous cell carcinoma (HNSCC). We tested the effect of EphB4-specific siRNA and antisense oligonucleotides (AS-ODN) on cell growth, migration and invasion, and the effect of EphB4 AS-ODN on tumor growth in vivo. All HNSCC tumor samples express EphB4 and levels of expression correlate directly with higher stage and lymph node metastasis. Six of 7 (86%) HNSCC cell lines express EphB4, which is induced either by EGFR activation or by EPHB4 gene amplification. EphrinB2 was expressed in 65% tumors and 5 of 7 (71%) cell lines. EphB4 provides survival advantage to tumor cells in that EphB4 siRNA and AS-ODN significantly inhibit tumor cell viability, induce apoptosis, activate caspase-8, and sensitize cells to TRAIL-induced cell death. Furthermore, EphB4-specific AS-ODN significantly inhibits the growth of HNSCC tumor xenografts in vivo. Expression of EphB4 in HNSCC tumor cells confers survival and invasive properties, and thereby provides a strong rationale for targeting EphB4 as novel therapy for HNSCC. |
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Keywords: | EphB4 angiogenesis tumor survival apoptosis migration |
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