Evaluation of the Role of ITGBL1 in Ovarian Cancer

SIMPLE SUMMARY: A poorly characterized protein called Integrin beta-like 1 (ITGBL1) may play an important role in ovarian cancer progression. Our previous studies have indicated that increased expression of the gene coding for ITGBL1 is related to poor prognosis for ovarian cancer patients. In the present study we investigated the role of ITGBL1 in ovarian cancer cells using several in-vitro assays and global gene expression analysis. We found that ITGBL1 overexpression affected cellular adhesion, motility and invasiveness. In addition, ITGBL1 caused cells to be more resistant to cisplatin and paclitaxel, major drugs used in ovarian cancer treatment. Our results indicate that higher expression of ITGBL1 in ovarian cancer is associated with the features that may worsen the clinical course of the disease. Further studies will show if ITGBL1 can be exploited as a cancer biomarker and/or molecular target for experimental biological therapy. 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 Integrin beta-like 1 (ITGBL1), 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 ITGBL1 mRNA isoforms in five OC cell lines. OAW42 and SKOV3, having the lowest level of any ITGBL1 mRNA, were chosen to produce ITGBL1-overexpressing variants. In these cells, abundant ITGBL1 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 ITGBL1 overexpression affected cellular adhesion, migration and invasiveness, while it had no effect on proliferation rate and the cell cycle. ITGBL1-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 ITGBL1 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 ITGBL1 in OC is associated with features that may worsen clinical course of the disease.