A Potential Ovarian Cancer Therapeutic Antibody Targeting Tumor-Specific Glycans on Periostin
Abstract
Introduction and Objective. Ovarian cancer (OC) is a common cause of death globally (death rate 6.7 per 100,000 women per year, 5-year survival 49.1%). New therapeutic approaches are needed to improve OC outcomes. Periostin (POSTN) is a secreted extracellular matrix protein overexpressed in OC, contributing to cell proliferation and metastasis. Antibodies that blocks POSTN could be less toxic and more effective than conventional treatments. Our study investigated whether the human single-chain variable fragment POSTN antibody (scFvC9-Fc) that targets the bisecting N-glycan structure of POSTN expressed in OC cells can block POSTNs metastatic function. Methods. We used OVCAR3 cells (OC cells) from high-grade serous ovarian adenocarcinoma to compare 4 exposures: POSTN complexed to scFvC9-Fc (1:1 ratio), POSTN alone, scFvC9-Fc complexed to bovine serum albumin (BSA - 1:1 ratio), and OVCAR3 cells alone (control). There were 3 samples of each exposure (n = 12). A scratch wound assay was used to assess cell migration over time measuring the area of gap at 0 and 48 hours. Analysis using SPSS was done to calculate mean, standard deviation and 95% CI’s of change in gap areas. An Independent-Samples Kruskal-Wallis Test was chosen to compare the change in gap area between groups. Results. No statistically significant difference was found in the change of area of gap among OC cells exposed to POSTN and scFvC9-Fc (-37,605 µm2, 95% CI -706,625 to 631,413) when compared to those exposed to POSTN (95,485, 95% CI -462,365 to 653,336), to BSA and scFvC9-Fc (268,520, 95% CI 144,814 to 392,226) and OC cells alone (94,839, 95% CI -320,001 to 509,679). There was a large degree of variability among the measurements. Conclusions-Implications. It is unclear whether the human POSTN antibody that targets the unique bisecting N-glycan structure found on POSTN could block the metastatic and migratory functions of POSTN. Future research should use larger sample sizes and standardized approaches for measuring the migratory changes of OC cells that are treated with single-chain variable fragment antibodies to determine their therapeutic significance.
Keywords
Periostin, single-chain variable fragment antibody, ovarian cancer, metastasis, bisecting N-glycan
Presentation Type
Poster Presentation
A Potential Ovarian Cancer Therapeutic Antibody Targeting Tumor-Specific Glycans on Periostin
Introduction and Objective. Ovarian cancer (OC) is a common cause of death globally (death rate 6.7 per 100,000 women per year, 5-year survival 49.1%). New therapeutic approaches are needed to improve OC outcomes. Periostin (POSTN) is a secreted extracellular matrix protein overexpressed in OC, contributing to cell proliferation and metastasis. Antibodies that blocks POSTN could be less toxic and more effective than conventional treatments. Our study investigated whether the human single-chain variable fragment POSTN antibody (scFvC9-Fc) that targets the bisecting N-glycan structure of POSTN expressed in OC cells can block POSTNs metastatic function. Methods. We used OVCAR3 cells (OC cells) from high-grade serous ovarian adenocarcinoma to compare 4 exposures: POSTN complexed to scFvC9-Fc (1:1 ratio), POSTN alone, scFvC9-Fc complexed to bovine serum albumin (BSA - 1:1 ratio), and OVCAR3 cells alone (control). There were 3 samples of each exposure (n = 12). A scratch wound assay was used to assess cell migration over time measuring the area of gap at 0 and 48 hours. Analysis using SPSS was done to calculate mean, standard deviation and 95% CI’s of change in gap areas. An Independent-Samples Kruskal-Wallis Test was chosen to compare the change in gap area between groups. Results. No statistically significant difference was found in the change of area of gap among OC cells exposed to POSTN and scFvC9-Fc (-37,605 µm2, 95% CI -706,625 to 631,413) when compared to those exposed to POSTN (95,485, 95% CI -462,365 to 653,336), to BSA and scFvC9-Fc (268,520, 95% CI 144,814 to 392,226) and OC cells alone (94,839, 95% CI -320,001 to 509,679). There was a large degree of variability among the measurements. Conclusions-Implications. It is unclear whether the human POSTN antibody that targets the unique bisecting N-glycan structure found on POSTN could block the metastatic and migratory functions of POSTN. Future research should use larger sample sizes and standardized approaches for measuring the migratory changes of OC cells that are treated with single-chain variable fragment antibodies to determine their therapeutic significance.