PUBLICATION

ICAM1 (CD54) Contributes to the Metastatic Capacity of Gastric Cancer Stem Cells

Authors
Tinajero-Rodríguez, J.M., Ramírez-Vidal, L., Becerril-Rico, J., Alvarado-Ortiz, E., Romero-Rodríguez, D.P., López-Casillas, F., Hernández-Sotelo, D., Fernández-Ramírez, F., Contreras-Paredes, A., Ortiz-Sánchez, E.
ID
ZDB-PUB-240901-10
Date
2024
Source
International Journal of Molecular Sciences   25(16): (Journal)
Registered Authors
Keywords
cancer stem cell, gastric cancer, metastasize, tumorigenic
MeSH Terms
  • Drug Resistance, Neoplasm*/genetics
  • Animals
  • Neoplasm Metastasis
  • Cell Movement*
  • Zebrafish*
  • Neoplastic Stem Cells*/metabolism
  • Neoplastic Stem Cells*/pathology
  • Humans
  • Stomach Neoplasms*/genetics
  • Stomach Neoplasms*/metabolism
  • Stomach Neoplasms*/pathology
  • Cisplatin/pharmacology
  • Cell Line, Tumor
  • STAT3 Transcription Factor/genetics
  • STAT3 Transcription Factor/metabolism
  • Intercellular Adhesion Molecule-1*/genetics
  • Intercellular Adhesion Molecule-1*/metabolism
PubMed
39201551 Full text @ Int. J. Mol. Sci.
Abstract
Gastric cancer is the fourth leading cause of cancer deaths worldwide. The presence of chemoresistant cells has been used to explain this high mortality rate. These higher tumorigenic and chemoresistant cells involve cancer stem cells (CSCs), which have the potential for self-renewal, a cell differentiation capacity, and a greater tumorigenic capacity. Our research group identified gastric cancer stem cells (GCSCs) with the CD24+CD44+CD326+ICAM1+ immunophenotype isolated from gastric cancer patients. Interestingly, this GCSC immunophenotype was absent in cells isolated from healthy people, who presented a cell population with a CD24+CD44+CD326+ immunophenotype, lacking ICAM1. We aimed to explore the role of ICAM1 in these GCSCs; for this purpose, we isolated GCSCs from the AGS cell line and generated a GCSC line knockout for ICAM1 using CRISPR/iCas9, which we named GCSC-ICAM1KO. To assess the role of ICAM1 in the GCSCs, we analyzed the migration, invasion, and chemoresistance capabilities of the GCSCs using in vitro assays and evaluated the migratory, invasive, and tumorigenic properties in a zebrafish model. The in vitro analysis showed that ICAM1 regulated STAT3 activation (pSTAT3-ser727) in the GCSCs, which could contribute to the ability of GCSCs to migrate, invade, and metastasize. Interestingly, we demonstrated that the GCSC-ICAM1KO cells lost their capacity to migrate, invade, and metastasize, but they exhibited an increased resistance to a cisplatin treatment compared to their parental GCSCs; the GCSC-ICAM1KO cells also exhibited an increased tumorigenic capability in vivo.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping