In order to find targets for treatment of tumors, researchers often look for specific differences between cancer cells and normal cells. A study now shows that the lipid metabolism in colon cancer cells is significantly changed compared to healthy tissue. The results could potentially lead to treatment approaches that aim to cut off the energy supply to the tumor. They can also help to better predict the course of the disease in patients.
Colon cancer is one of the most common types of cancer worldwide and is responsible for the second largest number of cancer deaths after lung cancer. Although early detection and treatment options have improved over the past few decades, the five-year survival rate for patients with metastatic colorectal cancer is only ten to 14 percent. Due to their increased division rate, colon cancer cells need more fat-like molecules, so-called lipids, to build up their cell membranes and secure their energy supply compared to healthy cells. Earlier studies have already indicated that a specific signature of the cancer cells could be derived from this. However, the results were inconsistent.
Tumor cells with a specific signature
In order to check the thesis and thus possibly lay the foundation for new treatment approaches, a team led by Josef Ecker from the Technical University of Munich has now examined tissue samples from 106 colon cancer patients from whom the tumor was surgically removed. In addition, healthy tissue samples were available from 41 of these patients to serve as a comparison. With the help of mass spectroscopy, the researchers analyzed the proportion of around 200 different lipids in the respective samples.
The result: “We found significant differences between tumor and normal tissue for different types of lipids,” the researchers report. To rule out that the findings were only incidental, they compared the results with two independent cohorts of 20 and 28 colon cancer patients, from whom samples from the tumor and healthy tissue were also available. And indeed: “In all three independent cohorts, characteristic changes were found in the tumor tissue in two types of lipids, the sphingolipids and the glycerolipids,” said the researchers.
Differences at the genetic level
“In a sense, this is a fingerprint that can be used to very reliably distinguish cancer cells from normal cells,” explains Janssen. “This signature also has prognostic significance, so it allows statements about the course of the disease.” It was shown that certain patterns of triacylglycerol lipids were associated with how long a patient could live tumor-free after the operation and whether the tumor spread via the lymphatic system .
In addition, Ecker and his colleagues also analyzed the genetic properties of the tumor cells. They found that genes that code enzymes for the production of lipids were significantly more active in tumor cells. They were also able to confirm this result in mice. “This could result in new types of cancer therapy that directly address the changed metabolism of the tumor,” says Janssen. The idea: if it were possible to inhibit the corresponding enzymes with medication, cancer cells would be much more affected than normal body cells. In this way, the energy supply to the tumor could possibly be cut off and its growth limited.
Lipids as Biomarkers?
Some of the lipid signatures that the researchers identified as typical of tumors could also serve as biomarkers in diagnosing the disease. So far, such analyzes have been difficult. “Lipids in tissue samples are particularly sensitive molecules, some of which change quickly and break down easily,” explains Janssen. This could also explain the ambiguous results of previous studies on the subject. For the current study, the tissue samples were shock-frozen immediately after removal in order to prevent shifts in the lipid composition.
In clinical practice, such a method would be too costly to establish itself as a diagnostic standard. However, Ecker and his colleagues were able to identify some lipids that remain stable in the tissue samples even after removal and could therefore be suitable as biomarkers. “A better understanding of the cancer-associated glycerolipid and sphingolipid metabolism can thus lead to new strategies when it comes to diagnosing and treating colon cancer and predicting the course of the disease,” the researchers say.
Source: Josef Ecker (Technical University of Munich, Germany) et al., Gastroenterology, doi: 10.1053 / j.gastro.2021.05.009