Abstract 323: High grade serous ovarian cancer cells spontaneously self-organize in vitro into multicellular irregular aggregates and highly organized spheroids.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Ovarian cancer (OvCa) has the worst prognosis among gynecologic cancers because it is typically detected at an advanced stage. Accumulation of fluid inside the peritoneal cavity, and multicellular clusters featured within ascites are common manifestations of the disease. Patients undergo aggressive cytoreductive surgery followed by platinum-taxane therapy; yet in most cases, patients will relapse and die due to tumor progression. OvCa recurs as it presents, with growths within the peritoneal cavity, accumulation of ascites, but with a chemotherapy-resistant phenotype. Thus, understanding the dynamics of peritoneal metastases is of clear significance. This work provides evidences that OvCa cells derived from serous, treatment-resistant relapsed disease spontaneously develop multicellular anchorage-independent OvCa aggregates in vitro. The human serous ovarian adenocarcinoma PEO6 cells, while growing as adherent monolayer, spontaneously self-assemble into multicellular foci that float away off the adherent component of the culture. The floating phenotype is comprised of irregular cellular clusters and more organized spheroids with blastocyst-like morphology. Within each multicellular structure cells gather differently as evidenced by the distribution pattern of the cell junction adhesion molecule E-cadherin. Both types of non-adherent multicellular aggregates have live cells with no morphological features of apoptosis indicating their resistance to anoikis. Anchorage independent OvCa spheroids have the capacity to recreate the entire culture phenotype when placed in a new dish; the spheroids adhere upon transference and develop foci that grow upright irregular aggregates and more organized spheroids, ultimately leading to the generation of new non-adherent components. The floating PEO6 structures include clusters of cells expressing the cancer initiating antigen CD133 supporting their plasticity to perpetuate the anchorage-independent component of the culture. In summary, this study led to the characterization of an in vitro model of recurrent, treatment-resistant serous OvCa cells with intrinsic ability to gather in two types of clusters that survive in an anchorage-independent manner-a hallmark of transformation and critical factor in metastasis. The spontaneous in vitro development of OvCa multicellular irregular aggregates and spheroids at recurrence may represent a preclinical model to study the biology of selection and adaptation of disease malignancy and ways to interrupt its progression. Citation Format: Alicia A. Goyeneche. High grade serous ovarian cancer cells spontaneously self-organize in vitro into multicellular irregular aggregates and highly organized spheroids. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 323. doi:10.1158/1538-7445.AM2013-323