Abstract
Abstract Polyploid giant cancer cells (PGCCs) have been observed by pathologists for over a century. PGCCs or nuclear atypia are an important diagnosis feature for high grade serous carcinoma and frequently present in post-chemotherapy patients and contribute to tumor heterogeneity, but their functions are largely undefined. Little attention has been given to these cells, largely because PGCCs have been generally thought to originate from repeated mitosis/cytokinesis failure and have no capacity for long-term survival and cell proliferation. Here we report that we successfully purified and cultured PGCCs from human ovarian cancer cell lines and primary ovarian cancer. These cells are highly resistant to oxygen deprivation and could form through endoreduplication or cell fusion, generating regular-sized cancer cells through budding or burst. They are positive for normal and cancer stem cell markers, divided asymmetrically and cycled slowly. They can differentiate into adipose, cartilage, bone, and erythroid cells. A single PGCC formed cancer spheroids in vitro and generated tumors in immunodeficient mice. PGCC-derived tumor gained a mesenchymal phenotype with increased expression of cancer stem cell markers CD44 and CD133 and become more resistant to the treatment of cisplatin. Together, our results reveal that the PGCCs present a resistant form of human cancer cells like mother cancer stem cells that can contribute to generation of daughter cancer stem-like cells. The PGCCs may play a fundamental role in regulating tumor heterogeneity, stemness, and chemoresistance in human cancer. In contrast to the phenotype unstable cancer stem cells selected by cell surface markers, PGCCs can be stably passaged and maintained, thus these cells provide reproducible experimental system to study mechanisms involved in generation of ovarian cancer stem cells. Citation Format: Jinsong Liu. Giant cancer stem cells of high-grade ovarian serous carcinoma . [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B49.
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