EACR25-1619

Oncogenic Molecular Features triggered by the Mechanoresponsive Polycystin proteins

A. Gargalionis1, A. Giannopoulou2, P. Sarantis2, P. Korkolopoulou3, C. Piperi2, E. Lakiotaki3, A. Stofas3, S. Korfias4, E. Boviatsis5, A. Papavassiliou2
1National and Kapodistrian University of Athens, Medical School, Laboratory of Clinical Biochemistry, Athens, Greece
2National and Kapodistrian University of Athens, Medical School, Department of Biological Chemistry, Athens, Greece
3National and Kapodistrian University of Athens, Medical School, First Department of Pathology, Athens, Greece
4National and Kapodistrian University of Athens, Medical School, Department of Neurosurgery, Evaggelismos General Hospital, Athens, Greece
5National and Kapodistrian University of Athens, Medical School, Second Department of Neurosurgery, Athens, Greece
Introduction:

Mechanical cues regulate key features of cancer cells. Polycystin-1 (PC1) and polycystin-2 (PC2) are critical proteins that mediate mechanotransduction in cells. The aim was to investigate the impact of PC1 and PC2 on solid tumors.

Material and method:

The expression of polycystins was investigated immunohistochemically in archival material of human breast, glioma, and prostate tumors. Functional assays were performed on corresponding neoplastic cell lines. Xenografts of the respective human tumors were developed in immunosuppressed mice.

Result and discussion:

There are significant positive correlations between PC1 and PC2 expression in all tumor types, between PC2 expression and glioma grade, PC1 and PD-L1 expression in lung cancer, PC1 with extraprostatic extension and stage in prostate cancer (p<0.05). Functional assays on respective cancer cell lines showed that PC1 gene (PKD1) silencing or PC1 protein’s functional inhibition with a specific antibody decreased the clonogenic and migration potential of cancer cells. The A-549 and PC3 cancer cell lines were used to perform xenografts for lung and prostate cancer, respectively, and then the NSG mice were split into control and treated groups with PC-1 inhibitor. After tumor extraction, a 28.09% reduction in volume was observed in treated lung xenografts and a 1.53-fold reduction in tumor weight (p=0.071). Then, immunohistochemistry was performed for markers for epithelial to mesenchymal transition such as E-cadherin, cytokeratins and vimentin. E-cadherin and cytokeratins present increased expression while vimentin was decreased in treated mice (p=0.018, p=0.004 and p=0.011 respectively). In treated xenografts of the prostate cancer there was a reduction in volume by 18.12% and a decrease in weight by 1.39 times (p=0.27). An increase in E-cadherin and cytokeratins was found in treated mice (p=0.008, p=0.005 respectively)

Conclusion:

In conclusion, our data suggest that polycystins are involved in the development of solid tumors and influence disease progression, potentially acting as oncogenes. The research project was supported by the Hellenic Foundation for Research and Innovation (H.F.R.I.) under the “2nd Call for H.F.R.I. Research Projects to support Faculty Members & Researchers” (Project Number: 3226).