The finding was reported in the International Journal of Cancer.
Cancer is defined as the uncontrolled growth of body cells that results in the formation of tumours, which is caused by the accumulation of mutations in a cell’s genome. Tumor cells undergo a series of transformations that involve interactions between the body’s immune system and the tumour in order to become malignant, metastasizing cancer. However, many mechanistic details in this process remain unknown, making cancer prevention and treatment notoriously difficult.
Yet there is growing evidence that inflammation of blood vessel-lining “endothelial” cells is a key process in tumour progression to metastasis.
A key molecule for cancer metastasis has been identified as a molecule also involved in cardiovascular disease, implying a possible treatment approach for both diseases at the same time.
Worried about the biochemical mechanism underlying this process in cancer malignancy, a group of Hokkaido University researchers led by Professor Kyoko Hida discovered that in malignant tumours, endothelial cells accumulate a lipid delivery molecule known as “low-density lipoprotein” (LDL) and attract immune cells known as “neutrophils.” Neutrophils are immune suppressor cells that have been linked to cancer progression.
Previous research by the team revealed that blood vessels in malignant tumours expressed a high level of proteoglycans, and cancerous tissue is known to be inflamed. These characteristics are similar to those seen in atherosclerosis, and the researchers wanted to see if the similarities were deeper.
In contrast to non-metastasizing tumours, metastasizing tumours accumulate proteoglycan molecules, which attach to and accumulate LDL on the walls of blood vessels. The LDL that is bound is oxidised. Its receptor, known as “LOX-1,” is also abundant in the blood vessel-lining endothelial cells of metastasizing tumours. They discovered that this causes these cells to produce inflammatory signals that attract neutrophils. They then demonstrated that LOX-1 suppression can significantly reduce tumour malignancy in mice, as well as that LOX-1 overexpression causes an increase in signalling molecules that attract neutrophils. This sequence of interactions observed in malignant tumours, as the team hypothesised, is not novel: it occurs in atherosclerosis, the hardening of blood vessels.
“Atherosclerosis and cancer appear to be completely different diseases, but they share several common pathophysiological features in the blood vessels,” said Professor Kyoko Hida, Hokkaido University.
Despite the fact that some questions remain unanswered, particularly regarding the mechanism by which neutrophils contribute to cancer malignancy, this study is the first to explicitly prove the mechanistic similarities between cardiovascular disease and cancer progression and to trace the mechanism involving LDL accumulation and LOX-1 expression in in-vivo tumour tissue.
“Our present study focused on the importance of LOX-1 in endothelial cells as a common factor between cancer and atherosclerosis,” Hida explains. “The presence of neutrophils in tumors is a telltale sign of tumor progression.”
The research also shows that attacking neutrophil recruitment to endothelial cells may be an encouraging option to treat and preventing cancer and cardiovascular disease.
Hida concludes: “The number of patients with cancer who die not of cancer, but cardiovascular events, is increasing. Targeting the LOX-1/oxidized LDL axis might be a promising strategy for the treatment of the two diseases concomitantly.”