The Hidden Supporter Of Cancer: Your Fat

Fat has more energy per pound than any other nutritional substance. It's not surprising, then that some cancer cells have a preference to grow in fat tissues.

According to a new study by researchers at the Sloan Kettering Institute (SKI) at Memorial Sloan Kettering (MSK), melanomas prefer to grow near adipose (fat) tissue. Richard White (a surgeon-scientist from the Cancer Biology and Genetics Program, SKI), led the team. He found that melanomas will actively consume lipids and migrate to fat-rich tissues.

White said, "This hypothesis is about the seed-and soil hypothesis." "Tumor cells love to find fertile soil. We believe that the adipose tissues can offer melanoma very rich soil, based on our findings.

It is possible that the fat cells in some cancer cells can help them grow and spread. This new insight sheds more light on the connection between obesity, cancer, and may offer new treatments. Cutting off fat supplies could help fight certain types of cancer.

Follow the Fat

White and his coworkers did not intend to link fat with cancer. They simply happened upon it.

His team uses zebrafish as a model system for studying skin cancer. These melanomas are very similar in size to the ones found in people. It is also possible to monitor the progression of tumors by looking at them through their transparent eyes.

White says, "We ran a screen to see what was allowing melanoma cell growth in particular locations." We found many changes in gene expression that control how cells use cholesterol in melanoma cells at metastatic locations.

This led to additional questions. Did cancer cells make their own fats, or were they importing them from the nearby adipocytes? Oder were they getting them from nearby fat cells (adipocytes)?

Maomao, a postdoctoral fellow Maomao Zhu used fluorescent markers to identify lipids in the adipocytes. Then she put together the melanoma and adipocyte cells in a dish, and tracked their movements. Evidently, the lipids were consumed by the melanoma cell.

The same happened in fish. Zhang injected the melanoma cell lines next to zebrafish adipocytes. The cells also became lipid-rich. Furthermore, more than half of the metastasized melanoma cell metastatically to other locations migrated to adipocytes.

White's laboratory examined samples of tumors from patients with melanoma treated at MSK to further verify the hypothesis. Like zebrafish's cells, human cancer cells had fat-deposits.

Rich soil is essential for growth of cancer

In studying this connection, researchers found that consuming fat changed the cancer cells' behavior. The ability to break down collagen and cross the membranes in fat-fueled melanoma cell lines was enhanced, which allowed them to spread faster. The cells also had a modified metabolism that allowed them to burn more fat instead of sugar.

They wondered if blocking the ability of melanoma to take in fat could reduce its aggression. They tested the hypothesis by using a drug that blocks a protein called FATP transporter. This allows cancer cells to absorb fat. The drug is more effective in cancer cells because they have more of the protein than normal cells. The cells were unable to absorb fat, which led to slower growth.

White believes the findings could lead to a new approach for treating melanoma. White says it is possible to identify patients who are particularly lipid-dependent. He says that those patients might benefit from an approach to block fat uptake in the cells.

Obesity & Cancer

Although researchers have identified obesity as a major risk factor for the development of cancer, they still don't know how to connect it. While White's study doesn't directly address the matter, he says it does show a concrete link between lipids and cancer growth. It adds one more piece to what will likely be a large puzzle.

It is possible to reduce the risk of melanoma by changing one's diet. This is something that our team is keen on exploring.

The study shows the utility of model systems like zebrafish for studying cancer, and the advantage of a place like MSK, where basic scientists and clinicians can easily collaborate. Project co-authors were Travis Hollmann (MSK), Jedd Wolchok (MSK) and Charlotte Ariyan (MSK).

White says, "We began this in the Zebrafish and were then able to continue it to human tissue." It would have been difficult to do this at another institution.