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

Area of Science:

• Oncology
• Cell Biology
• Immunology

Background:

• Gastric cancer is a leading cause of cancer mortality globally, often driven by chemoresistant cancer stem cells (CSCs).
• Gastric cancer stem cells (GCSCs) with a CD24+CD44+CD326+ICAM1+ immunophenotype were identified in patients, distinct from healthy individuals.
• The role of ICAM1 in GCSC behavior remained largely unexplored.

Purpose of the Study:

• To investigate the function of ICAM1 in gastric cancer stem cells (GCSCs).
• To determine ICAM1's impact on GCSC migration, invasion, chemoresistance, and tumorigenicity.

Main Methods:

• GCSCs were isolated from the AGS cell line and engineered to be ICAM1-knockout (GCSC-ICAM1^KO) using CRISPR/iCas9.
• In vitro assays assessed migration, invasion, and chemoresistance (cisplatin).
• In vivo studies in a zebrafish model evaluated migratory, invasive, and tumorigenic properties.

Main Results:

• ICAM1 was found to regulate STAT3 activation (pSTAT3-ser727) in GCSCs, influencing their metastatic potential.
• GCSC-ICAM1^KO cells demonstrated significantly reduced migration, invasion, and metastasis.
• Conversely, GCSC-ICAM1^KO cells exhibited enhanced resistance to cisplatin and increased in vivo tumorigenicity.

Conclusions:

• ICAM1 plays a critical role in GCSC-mediated migration, invasion, and metastasis through STAT3 activation.
• Targeting ICAM1 may offer a novel therapeutic strategy for overcoming chemoresistance in gastric cancer.
• Loss of ICAM1 in GCSCs paradoxically increases chemoresistance and tumorigenicity, highlighting a complex role in cancer progression.