Abstract 6012: Cancer stem cells could be responsible for the chimeras of hematopoietic cells in the cancer microenvironment

Abstract

Abstract Development of cancer stem cells (CSCs) model from iPSCs for different types of cancers will help to investigate the tumorigenesis and designing new therapies applicable to CSCs. In this context, our lab has developed a novel method to generate CSCs from iPSCs under cancer microenvironment using conditioned medium from different cancer cell lines. In our previous study, BT549 cell line conditioned media was used to convert iPSCs to CSCs (miPSCs-BTcscs). Here, we investigated the potential of adherent CSCs converted from iPSCs to give hematopoietic like cells. Cancer stem cells, miPSCs-BTcscs, were obtained by conversion of miPSCs (iPS MEF-Ng-20D-17) cells in the presence of conditioned medium from breast cancer cell line BT549 cells followed by the primary culture of the tumor formed in Balb/c nude mice. The stemness and tumorigenicity of miPSCs-BTcscs cells had previously been confirmed. miPSCs-BTcscs cells were cultured on gelatin coated dish in absence of Leukemia Inhibitory Factor (LIF) and select undifferentiated cells was done using puromycin. Non-adherent cells (NACs) arising from adherent CSCs collected and their viability, the morphology and the expression of hematopoietic cells markers were investigated using Giemsa staining, flow cytometry, immunofluorescence staining, and RT-PCR. Moreover, to assess the potential of clonogenicity in vivo and the engraftment of NACs, NACs were injected into the tail vein of busulfan conditioned Balb/c nude mice. The round nucleated NACs were found to be viable, positive for Lin markers and CD34 and expressed hematopoietic markers just like homing to the bone marrow. When NACs were injected into a mouse, Wright-Giemsa staining showed that the number of white blood cells got higher than those in the control mice after 4 weeks. As conclusion, CSCs were demonstrated to have the potential to provide progenies with hematopoietic markers, morphology and homing ability to bone marrow, which could give a new insight into tumor microenvironment according to the plasticity of CSCs. Citation Format: Ghmkin Hassan, Said M Afify, Kazuki Kumon, Amira Osman, Maram H Zahra, Akimasa Seno, Masaharu Seno. Cancer stem cells could be responsible for the chimeras of hematopoietic cells in the cancer microenvironment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6012.