The oxidized-LDL/LOX-1 axis in tumor endothelial cells enhances metastasis by recruiting neutrophils and cancer cells

Takuya Tsumita, Nako Maishi, Dorcas Akuba Muhyia Annan, Mohammad Alam Towfik, Aya Matsuda, Yasuhito Onodera, Jin Min Nam, Yasuhiro Hida, Kyoko Hida

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Epidemiological relationships between cancer and cardiovascular diseases have been reported, but a molecular basis remains unclear. Some proteoglycans that strongly bind low-density-lipoprotein (LDL) are abundant both in atherosclerotic regions and in high metastatic-tumor tissue. LDL retention is crucial for the initiation of atherosclerosis, although its contribution to malignancy of cancer is not known. In our study, we show the importance of the accumulation of LDL in tumor metastasis. We demonstrated that high metastatic-tumor tissue contains high amounts of LDL and forms more oxidized LDL (ox-LDL). Interestingly, lectin-like ox-LDL receptor 1 (LOX-1), a receptor for ox-LDL and a recognized key molecule for cardiovascular diseases, was highly expressed in tumor endothelial cells (TECs). Neutrophils are important for ox-LDL formation. Since we observed the accumulation and activation of neutrophils in HM-tumors, we evaluated the involvement of LOX-1 in neutrophil migration and activation. LOX-1 induced neutrophil migration via CCL2 secretion from TECs, which was enhanced by ox-LDL. Finally, we show genetic manipulation of LOX-1 expression in TECs or tumor stroma tended to reduce lung metastasis. Thus, the LOX-1/ox-LDL axis in TECs may lead to the formation of a high metastatic-tumor microenvironment via attracting neutrophils.

Original languageEnglish
Pages (from-to)944-956
Number of pages13
JournalInternational Journal of Cancer
Volume151
Issue number6
DOIs
Publication statusPublished - 15-09-2022
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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