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Enzyme Makes Mesothelioma More Aggressive, Less Responsive to Treatment

What is mesotheliomaThere’s new evidence that a glycoprotein produced on the surface of some mesothelioma cells could have a major impact on disease progression and treatment outcomes – especially in patients with the biphasic form of the disease.

Biphasic mesothelioma accounts for about 20 to 35 percent of mesothelioma cases and is generally considered even more difficult to treat than the more common epithelioid mesothelioma. Now, a team of Italian researchers from the University of Torino say they have discovered one of the factors that may influence the aggressiveness of biphasic mesothelioma.

The focus of their new study is a molecule called CD157, an enzyme that has been associated with ovarian cancer. Because the epithelial cells of the ovaries and the cells of the mesothelium (where mesothelioma starts) share a common origin, the researchers surmised that CD157 may also be linked to mesothelioma.

Four of the nine malignant pleural mesothelioma cell lines tested had higher levels of CD157. The molecule was also overexpressed in 85.2% of mesothelioma tissue samples and was found to be correlated with clinical aggressiveness, particularly in biphasic mesothelioma. Raising or lowering the level of CD157 in mesothelioma cells affected their growth, their ability to migrate and invade other tissues, and their propensity to form tumors. All of these affects were more pronounced in the biphasic cells, in which higher CD157 expression also appeared to reduce sensitivity to platinum-based chemotherapy drugs.

In a report of their findings published in the journal Oncotarget, lead authors Dr. Erika Ortolan of the Laboratory of Immunogenetics and oncologist Dr. Alice Giacomino conclude, “These findings indicate that CD157 is implicated in multiple aspects of malignant pleural mesothelioma progression and suggest that CD157 expression could be used to stratify patients into different prognostic groups or to select patients that might benefit from a particular chemotherapeutic approach.”

Platinum-based chemotherapy is typically the first-line treatment for all mesothelioma patients, regardless of histological subtype.

Source:

Ortolan, E, “CD157 enhances malignant pleural mesothelioma aggressiveness and predicts poor clinical outcome”, July 8, 2014, Oncotarget, Epub ahead of print

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