Endothelial CLEC-1b plays a protective role against cancer hematogenous metastasis

• Published in: Biochemical and biophysical research communications Vol. 708; p. 149819
• Main Authors: Yamazaki, Ekura, Ikeda, Koji, Urata, Ryota, Ueno, Daisuke, Katayama, Akiko, Ito, Fumiaki, Ikegaya, Hiroshi, Matoba, Satoaki
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.05.2024
• Subjects: Aged; Aging; Animals; Blood Platelets - metabolism; Cancer; Cellular senescence; CLEC-1b; Endothelial cell; Hematogenous metastasis; Humans; Lectins, C-Type - genetics; Lectins, C-Type - metabolism; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mice; Neoplasms - metabolism; Transcription Factors - metabolism; Transendothelial and Transepithelial Migration; Hematogenous metastasis; Aging; Endothelial cell; CLEC-1b; Cellular senescence; Cancer
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2024.149819

Metastasis, which is the spread of cancer cells into distant organs, is a critical determinant of prognosis in patients with cancer, and blood vessels are the major route for cancer cells to spread systemically. Extravasation is a critical process for the hematogenous metastasis; however, its underlying molecular mechanisms remain poorly understood. Here, we identified that senescent ECs highly express C-type lectin domain family 1 member B (CLEC-1b), and that endothelial CLEC-1b inhibits the hematogenous metastasis of a certain type of cancer. CLEC-1b expression was enhanced in ECs isolated from aged mice, senescent cultured human ECs, and ECs of aged human. CLEC-1b overexpression in ECs prevented the disruption of endothelial integrity, and inhibited the transendothelial migration of cancer cells expressing podoplanin (PDPN), a ligand for CLEC-1b. Notably, target activation of CLEC-1b in ECs decreased the hematogenous metastasis in the lungs by cancer cells expressing PDPN in mice. Our data reveal the protective role of endothelial CLEC-1b against cancer hematogenous metastasis. Considering the high CLEC-1b expression in senescent ECs, EC senescence may play a beneficial role with respect to the cancer hematogenous metastasis. •CLEC-1b expression is enhanced in senescent endothelial cells.•Endothelial CLEC-1b prevents the disruption of endothelial integrity mediated by cancer cells.•Endothelial CLEC-1b prevents the transendothelial migration of cancer cells expressing PDPN.•Target activation of CLEC-1b in ECs inhibits the hematogenous metastasis of cancer in mice.