Abstract
Abstract Due to the high mortality caused by frequent relapse and metastasis in patients with ovarian cancer, advances in treatment remain necessary. In this study, we developed a chromatographical process which converted native protein human serum albumin (HSA) into a water-soluble nano-fibrillar protein structure and aimed to explore the potential inhibitory effect of fibrillar HSA (F-HSA) on ovarian tumor metastasis. Transwell migration assay, western blotting and gelatin zymography were used to investigate the effects of F-HSA in vitro. Its effects in vivo were evaluated in orthotopic and metastatic xenograft mouse models established using an SKOV3 ovarian cancer cell line that stably expressed green fluorescent protein and luciferase. The fibrillar structure of converted HSA was verified by transmission electron microscopy and Thioflavin T (ThT) fluorescence assay. Treatment with F-HSA decreased the viability, migration and invasion of several ovarian cancer cell lines in vitro. F-HSA bound to β1 integrin receptor to increase PTEN phosphorylation and decrease phosphorylation of FAK and Akt. The inhibitory effect of F-HSA on invasive ability of SKOV3 cells was associated with decreases in phosphorylation of Raf and Erk as well as changes in Crk phosphorylation leading to down-regulation of Rac and MMP2 activities. Orthotopic and metastatic xenograft mouse models showed that F-HSA treatment suppressed tumor growth and metastasis and prolonged survival of SKOV3-bearing mice. These results suggest that F-HSA may have great potential for development as a novel therapeutic agent for metastatic and drug-resistant ovarian cancer. Citation Format: Tai-An Chen, Shao-Wen Hung, Yu-Ching Chang, Chih-Yuan Chen, Hsin-Ying Hsieh, Chi-Ming Liang, Shu-Mei Liang. Fibrillar human serum albumin suppresses ovarian cancer metastasis by targeting β1 integrin and its downstream FAK signaling pathways. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A100.
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