Lung endothelial PEAR1 induces tumor cell dormancy

Area of Science:

• Oncology
• Cell Biology
• Molecular Biology

Background:

• Distant metastases develop years after initial cancer diagnosis, posing a significant clinical challenge.
• Understanding the mechanisms regulating dormant disseminated tumor cells (DTCs) is crucial for preventing metastasis.

Purpose of the Study:

• To identify endothelial proteins that regulate tumor cell dormancy.
• To elucidate the role of platelet and endothelial aggregation receptor 1 (PEAR1) in tumor cell dormancy and metastasis.

Main Methods:

• Screening of endothelial secreted and plasma membrane proteins.
• In vitro studies using human and murine endothelial cells and tumor cells.
• In vivo studies using PEAR1-deficient mice.

Main Results:

• PEAR1 was identified as a key regulator of tumor cell dormancy.
• Endothelial cells lacking PEAR1 failed to promote tumor cell dormancy.
• PEAR1 deficiency in mice reduced lung tumor cell dormancy and increased metastasis.
• PEAR1 induces dormancy by interacting with lysyl oxidase like 2 (LOXL2) and cathepsin D (CTSD).
• Suppression of CTSD expression increased tumor cell dormancy and decreased metastatic potential.

Conclusions:

• PEAR1 is essential for maintaining tumor cell dormancy.
• PEAR1 regulates dormancy via LOXL2 and CTSD.
• CTSD and LOXL2 are potential therapeutic targets to promote tumor dormancy and reduce metastasis.