Evaluation of the Role of ITGBL1 in Ovarian Cancer

Abstract

In our previous microarray study we identified two subgroups of high-grade serous ovarian cancers with distinct gene expression and survival. Among differentially expressed genes was an <i>Integrin beta-like 1</i> (<i>ITGBL1</i>), coding for a poorly characterized protein comprised of ten EGF-like repeats. Here, we have analyzed the influence of ITGBL1 on the phenotype of ovarian cancer (OC) cells. We analyzed expression of four putative <i>ITGBL1</i> mRNA isoforms in five OC cell lines. OAW42 and SKOV3, having the lowest level of any <i>ITGBL1</i> mRNA, were chosen to produce <i>ITGBL1</i>-overexpressing variants. In these cells, abundant <i>ITGBL1</i> mRNA expression could be detected by RT-PCR. Immunodetection was successful only in the culture media, suggesting that ITGBL1 is efficiently secreted. We found that <i>ITGBL1</i> overexpression affected cellular adhesion, migration and invasiveness, while it had no effect on proliferation rate and the cell cycle. <i>ITGBL1</i>-overexpressing cells were significantly more resistant to cisplatin and paclitaxel, major drugs used in OC treatment. Global gene expression analysis revealed that signaling pathways affected by <i>ITGBL1</i> overexpression were mostly those related to extracellular matrix organization and function, integrin signaling, focal adhesion, cellular communication and motility; these results were consistent with the findings of our functional studies. Overall, our results indicate that higher expression of <i>ITGBL1</i> in OC is associated with features that may worsen clinical course of the disease.