Abstract 1917: Re-thinking the concept of cancer stem cells: Polyploid giant cancer cells as mother cancer stem cells

Abstract

Abstract Polyploid giant cancer cells (PGCCs) have been observed by pathologists for over a century. PGCCs contribute to solid 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. Our group has recently reported 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 quickly 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, and bone. 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 and also form tissue organ-like structure. Together, our results reveal that the PGCCs present a resistant form of human cancer that behaves like mother cancer stem cells that can contribute to generation of daughter cancer stem-like cells and formation of tissue organ structure. These cells can be induced in response to hypoxia and 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 cancer stem cells. The key references related this concept are listed below. we will provide a most updated data to support this new concept that PGCCs as mother cancer stem cells at this meeting. Zhang S et al, Oncogene 2013, March online publication; Zhang S et al, Int J Cancer. 2013 Feb 1;134(3):508-18; Zhang S el al, Cancer Lett. 2013 Jun 10;333(2):205-12. Citation Format: Jinsong Liu, Imelda Mercado-Uribe, Na Niu, Baocun Sun, Jian Kuang, Shiwu Zhang. Re-thinking the concept of cancer stem cells: Polyploid giant cancer cells as mother cancer stem cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1917. doi:10.1158/1538-7445.AM2014-1917