RUNX1 promotes angiogenesis in colorectal cancer by regulating the crosstalk between tumor cells and tumor associated...

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Colorectal cancer (CRC) is a prevalent malignancy globally.
• Tumor angiogenesis and metastasis are key features of CRC.
• Runt-related transcription factor 1 (RUNX1) is implicated in CRC progression, metastasis, and chemoresistance.

Purpose of the Study:

• To investigate the role of RUNX1 in the crosstalk between CRC cells and M2-polarized tumor-associated macrophages (TAMs).
• To explore the relationship between RUNX1, M2 TAMs, and neoplastic angiogenesis in CRC.

Main Methods:

• Investigated RUNX1's role in recruiting and polarizing macrophages to M2 phenotype via chemokine (CCL2) production and Hedgehog pathway activation.
• Assessed the pro-angiogenic effects of platelet-derived growth factor (PDGF)-BB, a cytokine produced by M2 macrophages, in vitro and in vivo.
• Examined PDGF-BB's influence on RUNX1 expression, CRC cell migration, and invasion.

Main Results:

• RUNX1 promotes M2 TAM polarization in CRC by upregulating CCL2 and activating the Hedgehog pathway.
• PDGF-BB, secreted by M2 TAMs, stimulates angiogenesis and enhances RUNX1 expression, migration, and invasion in CRC cells.
• A positive feedback loop between RUNX1 and PDGF-BB was identified.

Conclusions:

• RUNX1 promotes CRC angiogenesis through the regulation of M2 macrophages within the tumor microenvironment.
• The findings suggest a potential combined therapeutic strategy targeting RUNX1 and TAM-derived PDGF-BB in CRC treatment.