12:00 AM
Apr 10, 2014
 |  BC Innovations  |  Cover Story

Pre-EMP-tive strike against GBM

University of California, Los Angeles researchers have treated glioblastoma in mice by inhibiting epithelial membrane protein 2.1 The findings open up a new indication for spinout Paganini Biopharma Inc., which has a mAb against the target in development for triple-negative breast cancer.

Epithelial membrane protein 2 (EMP2) is expressed in multiple tissues, including heart, lung, uterus and eye, in which it interacts with integrins to regulate adhesion between cells and the extracellular matrix.2,3

Over the past eight years, several UCLA teams led by Madhuri Wadehra showed that EMP2 was upregulated in endometrial, ovarian and breast cancers, in which it correlated with advanced disease and poor survival,4-7 and that inhibiting the protein reduced ovarian and breast tumor growth in mice.6,7

Based on a different group's gene expression research,8 Wadehra hypothesized that EMP2 also could be a target in glioblastoma multiforme (GBM)-the most common and aggressive form of brain cancer.

First, the team showed that EMP2 upregulation directly correlated with EMP2 levels in GBM. In a panel of samples from more than 300 patients with GBM, up to 95% of primary GBM tumors had higher levels of EMP2 than the surrounding normal brain tissue.

In addition, tumor levels of EMP2 correlated positively with activation of Src-an intracellular tyrosine kinase that contributes to cancer progression-and correlated negatively with patient survival.

In human GBM cell lines, EMP2 enhanced cell invasiveness by activating the integrin avb3 (CD51/CD61)-focal adhesion kinase (FAK)-Src signaling pathway. In mice injected intracranially with human GBM cell lines, imaging studies showed that tumors generated from EMP2 + cells were more invasive than tumors produced from cells in which EMP2 had been silenced with shRNA.

Lastly, the team tested two EMP2 inhibitors in mice...

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