Leptin enhances angiogenesis and vascular development in precancerous cells, according to study in Carcinogenesis.
Researchers from Michigan State University and Oakland University in Rochester, MI, discovered how leptin, a fat cell-derived hormone, may aid in the progression of colon cancer. They found that the hormone induced precancerous colon cells to increase production of a growth factor that enhances blood supply to early cancer cells promoting tumor growth and cancer progression.
The results appear in a paper called “Novel Mechanism for Obesity-induced Colon Cancer Progression” published in Carcinogenesis. The scientists studied leptin, which regulates body energy and is higher in obese individuals and has been linked to colon cancer. While leptin promotes angiogenesis in adipose tissue, it is unknown whether it can induce epithelial cells to produce factors that may drive angiogenesis, vascular development, and therefore cancer progression.
The scientists set out to compare the effects of leptin-stimulated colon epithelial cells on angiogenesis. The cells were taken from two mouse models, which differed in adenomatous polyposis coli (Apc) genotype, which is the gatekeeper tumor suppressor gene for colon cancer. They used ex vivo rat mesenteric capillary bioassay and human umbilical vein endothelial cell (HUVEC) models to study angiogenesis.
Cells from the mice that carried the Apc mutation when stimulated with leptin produced significantly more vascular endothelial growth factor (VEGF) than the cells from the other mouse model, according to the investigators. Leptin treatment induced dose-dependent increases in VEGF only in the mice with the Apc genotype. The enhanced capillary formation was blocked by the addition of a neutralizing antibody against VEGF.
These cells also had higher HUVEC cell proliferation, chemotaxis, upregulation of adhesion proteins, and cell-signaling activation resulting in nuclear factor kappa B nuclear translocation and DNA binding due to VEGF.
These findings show that leptin can induce preneoplastic colon epithelial cells to orchestrate VEGF-driven angiogenesis and vascular development.