CD24+CD44+CD54+EpCAM+ gastric cancer stem cells predict tumor progression and metastasis: clinical and experimental evidence

Stem Cell Research & Therapy

Research

Elizabeth Pérez-Islas¹  Roberto Herrera-Goepfert¹  Fernando López-Casillas²  Lizbeth Ramírez-Vidal³  Angel A. Gómez-Gallegos⁴  Jared Becerril-Rico⁴  Elizabeth Langley⁵  Zuly J. Hernandez-Peralta⁵  Elizabeth Ortiz-Sánchez⁵  Mariel E. Toledo-Guzmán⁵  Alejandro García-Carrancá⁶  Luis F. Oñate-Ocaña⁷  Angélica Hernández-Guerrero⁸ 

[1]Departamento de Patología, Instituto Nacional de Cancerología, Av. San Fernando 22, Colonia Sección XVI, Tlalpan, 14080, Mexico City, Mexico

[2]Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n Ciudad Universitaria, Coyoacán, 04510, Mexico City, Mexico

[3]Posgrado de Ciencias Biomédicas. Facultad de Medicina, Universidad Nacional Autónoma de México, Circuito Exterior s/n Ciudad Universitaria, Coyoacán, 04510, Mexico City, Mexico

[4]Posgrado en Ciencias Biológicas, Unidad de Posgrado, Edificio A, 1° Piso, Circuito de Posgrados, Ciudad Universitaria, C.P. 04510, Coyoacán, Distrito Federal, Mexico

[5]Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Av. San Fernando 22, Colonia Seccion XVI, Tlalpan, 14080, Mexico City, Mexico

[6]Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Av. San Fernando 22, Colonia Seccion XVI, Tlalpan, 14080, Mexico City, Mexico

[7]Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Av. San Fernando 22, Colonia Seccion XVI, Tlalpan, 14080, Mexico City, Mexico

[8]Unidad de Investigación en Cáncer, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico

[9]Subdirección de Investigación Clínica, Instituto Nacional de Cancerología, Av. San Fernando 22, Colonia Sección XVI, Tlalpan, 14080, Mexico City, Mexico

[10]Unidad de Endoscopia, Instituto Nacional de Cancerología, Av. San Fernando 22, Colonia Sección XVI, Tlalpan, 14080, Mexico City, Mexico

关键词: Gastric cancer;    Cancer stem cells;    Immunophenotype;    Metastasis;    Zebrafish;    Xenotransplants;   

DOI  :  10.1186/s13287-023-03241-7

 received in 2022-06-24, accepted in 2023-01-17,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundGastric cancer (GC) is a leading cause of cancer-related deaths worldwide. Specific and thorough identification of cancer cell subsets with higher tumorigenicity and chemoresistance, such as cancer stem cells (CSCs), could lead to the development of new and promising therapeutic targets. For better CSC identification, a complete or extended surface marker phenotype is needed to provide increased specificity for new cell targeting approaches. Our goal is to identify and characterize a putative extended phenotype for CSCs derived from patients with GC before treatment, as well as to evaluate its clinical value. In addition, we aim to ensure that cells with this phenotype have stemness and self-renewal capabilities.MethodsThis is a cohort study including 127 treatment-naïve patients with GC who attended the Instituto Nacional de Cancerología. Multiparametric flow cytometry analysis was performed to determine the extended phenotype of cells derived from gastric biopsies. The tumorigenic capability of cells identified in patients was assessed in a zebrafish model.ResultsCD24+CD44+CD54+EpCAM+ cells were present in all treatment-naïve patients included, with a median abundance of 1.16% (0.57–1.89%). The percentage of CD24+CD44+CD54+EpCAM+ cells was categorized as high or low using 1.19% as the cutoff for the CD24+CD44+CD54+EpCAM+ cell subset. Additionally, a higher TNM stage correlated with a higher percentage of CD24+CD44+CD54+EpCAM+ cells (Rho coefficient 0.369; p < 0.0001). We also demonstrated that a higher percentage of CD24+CD44+CD54+EpCAM+ cells was positively associated with metastasis. The metastatic potential of these cells was confirmed in a zebrafish model. Ultimately, under our conditions, we conclude that CD24+CD44+CD54+EpCAM+ cells are true gastric cancer stem cells (GCSCs).ConclusionThe CD24+CD44+CD54+EpCAM+ cells present in tissue samples from patients are true GCSCs. This extended phenotype results in better and more specific characterization of these highly tumorigenic cells. The relative quantification of CD24+CD44+CD54+EpCAM+ cells has potential clinical value, as these cells are associated with metastatic disease, making their presence an additional prognostic marker and possibly a target for the design of new antineoplastic treatments in the era of precision oncology. Overall, the extended CD24+CD44+CD54+EpCAM+ phenotype of GCSCs could support their isolation for the study of their stemness mechanisms, leading to the identification of better molecular targets for the development of both new therapeutic approaches such as oncoimmunotherapy and new diagnostic and clinical prognostic strategies for GC.

【 授权许可】

CC BY   
© The Author(s) 2023

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