The Ultrastructural Analysis of Human Colorectal Cancer Stem Cell-Derived Spheroids and Their Mouse Xenograft Shows That the Same Cells Types Have Different Ratios

Biology

Alessandra Boe¹  Giuseppe Familiari²  Michela Relucenti²  Selenia Miglietta²  Rui Chen³  Xiaobo Li³  Emanuela Pilozzi⁴  Maria Laura De Angelis⁵  Federica Francescangeli⁵  Ann Zeuner⁵  Vito D’Andrea⁶ 

[1] Core Facilities, Istituto Superiore di Sanità, 00161 Rome, Italy;Department of Anatomy, Section of Human Anatomy, Sapienza University of Rome, 00161 Rome, Italy;Department of Environmental Medicine and Toxicology, Southeast University, Nanjing 210096, China;Department of Experimental Medicine, Sant’Andrea Hospital, Sapienza University of Rome, 00185 Rome, Italy;Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy;Department of Surgical Sciences, Sapienza University of Rome, 00161 Rome, Italy;

关键词: spheroid;    xenotransplant;    cancer stem cell;    colorectal cancer;    electron microscopy;    flow cytometry;   

DOI  :  10.3390/biology10090929

来源: DOAJ

【 摘 要 】

Spheroids from primary colorectal cancer cells and their mice xenografts have emerged as useful preclinical models for cancer research as they replicate tumor features more faithfully as compared to cell lines. While 3D models provide a reliable system for drug discovery and testing, their structural complexity represents a challenge and their structure-function relationships are only partly understood. Here, we present a comparative ultrastructural and flow citometric analysis of patient colorectal cancer-derived spheroids and their mice xenografts. Ultrastructural observations highlighted that multicellular spheroids and their xenografts contain the same cancer cell types but with different ratios, specifically multicellular spheroids were enriched in cells with a stem-like phenotype, while xenografts had an increased amount of lipid droplets-containing cells. The flow cytometric analysis for stem cell marker and activity showed enrichment of stem-like cells presence and activity in spheroids while xenografts had the inverse response. Our results evidence the effects on cancer cells of different in vitro and in vivo microenvironments. Those differences have to be paid into account in designing innovative experimental models for personalized drug testing.

【 授权许可】

Unknown