Soluble IL-33 receptor sST2 inhibits colorectal cancer malignant growth by modifying the tumour microenvironment

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Interleukin-33 (IL-33) plays a role in the inflammatory tumor microenvironment and colorectal cancer (CRC) progression.
• The IL-33 receptor, ST2L, and its soluble form, sST2, are implicated in cancer development.

Purpose of the Study:

• To investigate the role of soluble ST2 (sST2) in colorectal cancer (CRC) progression and metastasis.
• To explore the potential of the IL-33/ST2L axis as a therapeutic target for CRC.

Main Methods:

• Assessed sST2 expression levels in human and mouse CRC cells with varying metastatic potential.
• Utilized gene knockdown and overexpression techniques to study sST2 function in CRC cells.
• Administered sST2-Fc fusion protein in mouse models of high-metastatic CRC.
• Analyzed the impact of sST2 on tumor growth, metastasis, angiogenesis, immune cell infiltration, and polarization.

Main Results:

• sST2 expression is inversely correlated with CRC malignancy and metastasis.
• Downregulation of sST2 promotes tumor growth, metastasis, and angiogenesis.
• Overexpression of sST2 inhibits these processes.
• sST2 administration reduces tumor growth, metastasis, and angiogenesis in vivo.
• sST2 suppresses IL-33-induced angiogenesis, Th1/Th2 responses, and M2a macrophage polarization.

Conclusions:

• sST2 acts as a negative regulator of CRC tumor growth and metastasis.
• sST2 exerts its effects by modifying the tumor microenvironment, including angiogenesis and immune cell activity.
• The IL-33/ST2L axis represents a promising therapeutic target for colorectal cancer treatment.