Fat fuels the road to cancer cell spread

December 26, 2016
cancer
Killer T cells surround a cancer cell. Credit: NIH

Cancer cells spread to other sites in the body through promoting the growth of new 'roads' to travel on. In a study to be published on December 26th in the top scientific journal, Nature, an international and multidisciplinary team of researchers, led by Prof. Dr. Peter Carmeliet (VIB-KU Leuven), discovered how a shift to increased fat utilization is required for the development and growth of these 'roads', termed lymphatic vessels - a special kind of blood vessels. This discovery paves the way towards developing therapeutics to limit lymphatic vessel growth in cancer by targeting fat utilization.

The spread of cancer, termed metastasis, is one of the most important and life-threatening complications of cancer today. Current chemotherapy and radiotherapy can effectively treat many cancers, however, the spread of to multiple sites within the body results in the majority of deaths associated with cancer. In order for cancer cells to spread, they must find a pre-existing 'road', or build a new 'road' to travel on. Lymphatic vessels, a specialized kind of vessels transporting fluid rather than blood, are a primary route of cancer cell spread, and the formation of new lymphatic vessels, termed lymphangiogenesis, is a poorly understood process, which currently lacks clinically approved drugs to prevent their growth during disease.

Fat fuels lymphatics

Expanding upon recent work in the laboratory published in top journals such as Cell and Nature, a team consisting of Drs. Brian Wong, Xingwu Wang and Annalisa Zecchin, guided by Prof. Carmeliet sought to investigate the nutrient utilization (metabolism) of lymphatic vessels. The study began with a simple observation: lymphatics use more fat (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.

What cells eat determines what they become

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 to lymphatics also change their 'taste' to prefer eating fat. The novelty of this discovery is that this 'transformation' relies on an increase of fat utilization. In this process, the fat is used to generate molecules which can modify important factors that regulate the expression of the genetic code, termed epigenetic changes, which can ensure the function of lymphatics. The hard-wiring of the genetic code (DNA) itself is not altered by fat, but the 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 next steps to preventing cancer cell spread and treating cancer patients

The immediate next steps of this research are clear and two-fold. On one hand, inhibitors of fat usage will be tested on a large scale for their ability to reduce metastasis in different types of cancer. On the other hand, 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 the debilitating swelling and dysfunction of the arms and legs, termed lymphedema, for which no drug is available.

Prof. Peter Carmeliet (VIB-KU Leuven): "Our immediate next studies are focusing on further translating these findings to the cancer setting. Previously, we could not develop drugs to target the growth of because we did not understand how they develop and function. Our work demonstrates the importance of their reliance on fat, and provides essential steps towards developing effective drugs to prevent excessive lymphatic growth in , but also to treat incapacitating complications of lymphedema."

Explore further: Restoring flawed tumor vessels could lead to better cancer treatments

More information: Brian W. Wong et al, The role of fatty acid β-oxidation in lymphangiogenesis, Nature (2016). DOI: 10.1038/nature21028

Related Stories

Restoring flawed tumor vessels could lead to better cancer treatments

November 17, 2016
Researchers led by Peter Carmeliet (VIB-KU Leuven) have found a novel way to normalize the dysfunctional blood vessels that are typical for tumors. Those vessels play a pivotal role in cancer metastasis, as their fragility ...

Origins of left-sided gut artery, lymphatic system discovered

December 16, 2014
Researchers have understood very little about how blood and lymphatic vessels form in the mammalian gut – until now.

How cancer tricks the lymphatic system into spreading tumors

May 11, 2015
Swollen lymph nodes are often the earliest sign of metastatic spread of cancer cells. Now cancer researchers and immunologists at Sweden's Karolinska Institutet have discovered how cancer cells can infiltrate the lymphatic ...

Chronic stress builds highways for cancer to spread

March 2, 2016
Monash University researchers have revealed that chronic stress builds lymphatic "highways" that provide cancer cells with a faster and more efficient way to spread.

Scientists reveal link between cell metabolism and the spread of cancer

October 20, 2016
Scientists at VIB and KU Leuven have discovered a crucial factor in the spread of cancer. A team led by professor Massimiliano Mazzone has demonstrated that the metabolism of macrophages, a particular type of white blood ...

Evidence strengthens link between NSAIDs and reduced cancer metastasis

February 13, 2012
A new study reveals key factors that promote the spread of cancer to lymph nodes and provides a mechanism that explains how a common over-the-counter anti-inflammatory medication can reduce the spread of tumor cells through ...

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.