Abstract 3655: Mapping the osteogenic lineage and identification of the cell of origin of osteosarcoma through high-dimensional analysis
Year: 2019
Type: conference-abstract
Abstract: Osteosarcoma (OS) is the most common primary malignant bone tumor in children and young adults. Neo-adjuvant chemotherapy combined with wide resection increased the 5-year survival rate to 60%-70%. However, treatment and outcome of OS have not changed in several decades. OS is histologically defined by the presence of malignant osteoid, suggesting it could be derived from anywhere in the osteogenic lineage between mesenchymal stem cells (MSC) and mature osteoblasts, but the cell of origin of OS is still undefined. Tracing the cells from which most cancers formed are characterized by its multipotent and/or unipotent stem cell nature. Studies on the cellular origin of tumors from phenotypic lineage-tracking and its derived progeny can reveal tissue-specific tumor-initiating cells. Investigating cell of origin of OS and osteogenic differentiation using developmentally relevant model using MSC to OB differentiation is promising. Here we developed a high-dimensional analytic pipeline using single-cell mass cytometry (CyTOF) and RNA sequencing to discover the unrecognized progenitor-osteoblast populations in the osteogenic lineage. For the data analysis, the population clustering using Flowsom and ConsensusClusterPlus on arcsinh transformed FCS data combined with t-SNE plot visualization shows that combination of CD49f, CD95, CD56, CD117 expression enables the identification and future isolation of the progenitor populations. Also, when comparing OS with the populations from MSC to OB, there are progenitor -osteoblast / mature osteoblast-like populations in tumor cells, but no MSC-like component is found. The expression level of CD56 and CD117 are significantly higher in OS compare to MSC and OB, which warrants future investigation of new therapeutic strategy. Isolation of the progenitor-osteoblast cells, gene expression comparison between OS and these progenitors, validation of their differentiation potential and tumor-initiating capacity is still underway. In this study, we developed a CyTOF based pipeline to discover the progenitor populations in the osteogenic lineage. By comparison of the OS and these progenitor cells, we may be able to unveil the cell of origin and new targeted treatment strategy of OS.Citation Format: Yifei Wang, Sankaranarayanan Kannan, Zhongting Zhang, Wendong Zhang, Michael Roth, Jonathan B. Gill, Zhaohui Xu, Xiangjun Tian, Jing Wang, Richard Gorlick. Mapping the osteogenic lineage and identification of the cell of origin of osteosarcoma through high-dimensional analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3655.
Source: Tumor Biology
Institution: The University of Texas MD Anderson Cancer Center
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,500
OpenAlex ID: W2955330478