Killer T cells surround a cancer cell. Credit: NIH
An international team discovered how a shift to increased fat utilization is required for the development and growth of lymphatic vessels for metastasis. This discovery paves the way towards developing therapeutics to limit lymphatic vessel growth in cancer by targeting fat utilization. Formation of new lymphatic vessels, ie lymphangiogenesis, is a poorly understood process, which currently lacks clinically approved drugs to prevent their growth during disease.
The study began with a simple observation: lymphatics use more fatty acids compared to blood vessels. This is the first description of the nutrient utilization of lymphatic vessels. Using drugs to prevent fat utilization by lymphatics prevented lymphatic growth, an important step in translating this finding to the cancer setting and inhibition of metastasis.
To understand why these cells are so reliant on fat, the researchers investigated how lymphatics develop. Lymphatics ‘transform’ from blood vessels during embryonic development, and this study shows that the signals that transform blood vessels to lymphatics also change their ‘taste’ to prefer eating fat. This ‘transformation’ relies on an increase of fat utilization. In this process, fat is used to generate molecules which can modify important factors that regulate expression of epigenetic changes, which can ensure the function of lymphatics. DNA itself is not altered by fat, but utilization of this code that defines the lymphatic gene signature is modulated. A key translational aspect to this finding was the proof that resupplying another (fat) nutrient source could restore the growth and function of lymphatics.
Dr. Brian Wong (VIB-KU Leuven): “Our study shows that the usage of fat by lymphatics is programmed in their development, and required for their growth and function. We have demonstrated by enhancing or preventing the usage of fat (or fat byproducts), we can control the growth of lymphatics.”
The immediate next steps are twofold: 1. Inhibitors of fat usage will be tested on a large scale for their ability to reduce metastasis in different types of cancer.
2. We will test whether dietary fat supplements (for instance in the form of ketone bodies, used by athletes) can heal faulty lymphatics, a major complication in cancer patients undergoing surgical cancer removal, which leads to lymphedema, with no drug available.
Prof. Peter Carmeliet said: “Our work demonstrates the importance of their reliance on fat, and provides essential steps towards developing effective drugs to prevent excessive lymphatic growth in cancer, but also to treat incapacitating complications of lymphedema.” http://www.vib.be/en/news/Pages/Fat-fuels-the-road-to-cancer-cell-spread.aspx
http://medicalxpress.com/news/2016-12-fat-fuels-road-cancer-cell.html
https://www.eurekalert.org/pub_releases/2016-12/vfi-fft122016.php
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