Evaluation of the Role of ITGBL1 in Ovarian Cancer.

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 (), 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 mRNA isoforms in five OC cell lines. OAW42 and SKOV3, having the lowest level of any mRNA, were chosen to produce -overexpressing variants. In these cells, abundant 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 overexpression affected cellular adhesion, migration and invasiveness, while it had no effect on proliferation rate and the cell cycle. -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 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 in OC is associated with features that may worsen clinical course of the disease.