CD24+CD44+CD54+EpCAM+ gastric cancer stem cells predict tumor progression and metastasis: clinical and experimental evidence
Por:
Gomez-Gallegos, Angel A., Ramirez-Vidal, Lizbeth, Becerril-Rico, Jared, Perez-Islas, Elizabeth, Hernandez-Peralta, Zuly J., Toledo-Guzman, Mariel E., Garcia-Carranca, Alejandro, Langley, Elizabeth, Hernandez-Guerrero, Angelica, Lopez-Casillas, Fernando, Herrera-Goepfert, Roberto, Oñate-Ocaña L.F., Ortiz-Sanchez, Elizabeth
Publicada:
3 feb 2023
Resumen:
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-naive patients with GC who attended the
Instituto Nacional de Cancerologia. 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-naive 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.
Filiaciones:
Posgrado en Ciencias Biológicas, Unidad de Posgrado, Edificio A, 1° Piso, Circuito de Posgrados, Ciudad Universitaria, Coyoacán, Distrito Federal, C.P. 04510, Mexico
Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Av. San Fernando 22, Colonia Seccion XVI, Tlalpan, Mexico City, 14080, Mexico
Posgrado de Ciencias Biomédicas. Facultad de Medicina, Universidad Nacional Autónoma de México, Circuito Exterior s/n Ciudad Universitaria, Coyoacán, Mexico City, 04510, Mexico
Departamento de Patología, Instituto Nacional de Cancerología, Av. San Fernando 22, Colonia Sección XVI, Tlalpan, Mexico City, 14080, Mexico
Unidad de Investigación en Cáncer, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Unidad de Endoscopia, Instituto Nacional de Cancerología, Av. San Fernando 22, Colonia Sección XVI, Tlalpan, Mexico City, 14080, Mexico
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito Exterior s/n Ciudad Universitaria, Coyoacán, Mexico City, 04510, Mexico
Subdirección de Investigación Clínica, Instituto Nacional de Cancerología, Av. San Fernando 22, Colonia Sección XVI, Tlalpan, Mexico City, 14080, Mexico
Unidad Posgrad, Posgrad Ciencias Biol, Edificio A,1 Piso,Ciudad Univ, Coyoacan 04510, Distrito Federa, Mexico
Inst Nacl Cancerol, Subdirecc Invest Basica, Ave San Fernando 22,Colonia Secc 16, Mexico City 14080, DF, Mexico
Univ Nacl Autonoma Mexico, Posgrad Ciencias Biomed, Fac Med, Circuito Exterior S-N Ciudad Univ, Mexico City 04510, DF, Mexico
Inst Nacl Cancerol, Dept Patol, Ave San Fernando 22,Colonia Secc 16, Mexico City 14080, DF, Mexico
Univ Nacl Autonoma Mexico, Unidad Invest Canc, Inst Invest Biomed, Mexico City 04510, DF, Mexico
Inst Nacl Cancerol, Unidad Endoscopia, Ave San Fernando 22,Colonia Secc 16, Mexico City 14080, DF, Mexico
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Circuito Exterior S-N Ciudad Univ, Mexico City 04510, DF, Mexico
Inst Nacl Cancerol, Subdirecc Invest Clin, Ave San Fernando 22,Colonia Secc 16, Mexico City 14080, DF, Mexico
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