Malignant mesothelioma is a rare asbestos-associated malignancy with limited therapeutic options. But recent research has concluded that Eprin (EPH) B2 seems to play an important role in malignant pleural mesothelioma cell lines and tumors.
Despite advances in treating malignant mesothelioma, the median survival remains 12 months from the time of diagnosis. This research project sought to increase understanding of the molecular basis for the diverse signaling pathways involved in cancer progression. Research like this should promote the discovery of novel biomarkers for early diagnosis and can potentially lead to more effective therapeutic tools for the disease.
Using expression arrays, the research team from New York University Langone Medical Center looked at EPHB2 in 34 malignant pleural mesothelioma tumors. EPHB2 was found to be elevated in tumor tissues compared with matched normal peritoneum. All cell lines of malignant pleural mesothelioma overexpressed EPHB2, but benign mesothelial cells did not. Also, EPHB2 was significantly elevated in malignant pleural mesothelioma tumor tissue when compared with matched normal peritoneum.
When EPHB2 was inhibited in cell lines, expression of matrix metalloproteinase and vascular endothelial growth factor were reduced, whereas caspase 2 and caspase 8 expression increased. Also, silencing EPHB2 increased apoptotic proteins and activity, along with decreasing scratch closure, proliferation, and invasion.
The researchers stated that targeting EPHB2 might provide a novel therapy to improve the prognosis in people suffering from malignant pleural mesothelioma. They suggested further in vivo investigations of specific inhibitors of EPHB2, with the goal of determining the importance of EPHB2 and its interactions with other receptor kinases and their ligands. EPHB2 might have a role as a marker of progression or worse prognosis for malignant pleural mesothelioma.
The study was published in the Journal of Thoracic Oncology (2013; doi: 10.1097/JTO.0b013e31829ceb6a).