The Ultrastructural Analysis of Human Colorectal Cancer Stem Cell-Derived Spheroids and Their Mouse Xenograft Shows That the Same Cells Types Have Different Ratios
Michela Relucenti,
Federica Francescangeli,
Maria Laura De Angelis,
Vito D’Andrea,
Selenia Miglietta,
Emanuela Pilozzi,
Xiaobo Li,
Alessandra Boe,
Rui Chen,
Ann Zeuner,
Giuseppe Familiari
Affiliations
Michela Relucenti
Department of Anatomy, Section of Human Anatomy, Sapienza University of Rome, 00161 Rome, Italy
Federica Francescangeli
Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy
Maria Laura De Angelis
Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy
Vito D’Andrea
Department of Surgical Sciences, Sapienza University of Rome, 00161 Rome, Italy
Selenia Miglietta
Department of Anatomy, Section of Human Anatomy, Sapienza University of Rome, 00161 Rome, Italy
Emanuela Pilozzi
Department of Experimental Medicine, Sant’Andrea Hospital, Sapienza University of Rome, 00185 Rome, Italy
Xiaobo Li
Department of Environmental Medicine and Toxicology, Southeast University, Nanjing 210096, China
Alessandra Boe
Core Facilities, Istituto Superiore di Sanità, 00161 Rome, Italy
Rui Chen
Department of Environmental Medicine and Toxicology, Southeast University, Nanjing 210096, China
Ann Zeuner
Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy
Giuseppe Familiari
Department of Anatomy, Section of Human Anatomy, Sapienza University of Rome, 00161 Rome, Italy
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.
