Scientists discover a new mechanism by which hypercholesterolemia promotes the development of bladder cancer

Scientists discover a new mechanism by which hypercholesterolemia promotes the development of bladder cancer

Scientists discover a new mechanism for hypercholesterolemia to promote the development of bladder cancer Scientists discover a new mechanism for hypercholesterolemia to promote the development of bladder cancer

Recently, the team of Huang Ruimin, a researcher from the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences, and the team of a young researcher Yan Jun from Fudan University, and the team of Professor Guo Hongqian from the Gulou Hospital of Nanjing University have discovered that oxidized low-density lipoprotein (ox-LDL) caused by hypercholesterolemia is regulated by The mechanism of tumor cell stemness, which in turn promotes the progression of bladder cancer
.

Related research results were published in Cancer Research

In today's society, changes in people's eating habits are one of the important reasons for the rapid increase in the number of people with metabolic syndrome in the world
.

Among them, hypercholesterolemia is a common metabolic disorder caused by an excessive increase in the level of low-density lipoprotein cholesterol in the plasma

In this study, the researchers first used two hypercholesterolemia mouse models (induced by high-fat and high-cholesterol feed or knocked out the Ldlr gene) to confirm that excess cholesterol in serum can increase bladder cancer transplanted tumors in mice As well as the tumor stemness of spontaneous bladder cancer, it promotes the development of bladder cancer
.

The hypercholesterolemia tumor-bearing mice treated with the selective cholesterol absorption inhibitor ezetimibe had significantly reduced tumor stemness and significantly slowed tumor growth, which suggests that the intake of cholesterol is the cause of the malignant increase in bladder cancer

Based on this, the research team analyzed the main components of cholesterol in serum, and finally focused on ox-LDL
.

Through further receptor verification and signal pathway analysis, the researchers found that ox-LDL can bind to bladder cancer cell membrane surface receptor CD36, affect the intracellular JAK2-STAT3 signaling pathway, and then regulate tumor cell stemness-related genes and promote bladder cancer cells Proliferate

This study established for the first time the relationship between hypercholesterolemia and bladder cancer, proposed that ox-LDL may be a risk factor for the progression of bladder cancer, and revealed that ox-LDL in the serum of patients with hypercholesterolemia is an external system An important factor that regulates tumor stem-like cells sexually provides a powerful example of the role of tumor macroenvironment in the regulation of tumor stemness
.

In addition, studies have also proposed that inhibiting cholesterol absorption, neutralizing serum ox-LDL, or targeting CD36/JAK2/STAT3 signaling pathways may become new intervention strategies for bladder cancer patients with hypercholesterolemia

The attending physician Yang Lin of Gulou Hospital Affiliated to Nanjing University and the assistant researcher Sun Jingya of Shanghai Institute of Medicine are the co-first authors of the paper; Yan Jun, Huang Ruimin, and Guo Hongqian are the co-corresponding authors of the paper
.

This research work was supported by the National Natural Science Foundation of China, the National Health Commission's major project for new drug creation, the Chinese Academy of Sciences and the Shanghai Science and Technology Commission

Related paper information: https://doi.

https://doi.
org/10.
1158/0008-5472.
CAN-21-0646