The trick tumors use to expand: survival at the expense of fat

Writing / Irene Vega

Recent research has shown that invasive cells are slower to proliferate but more resistant to therapies. So why do some invasive cells survive while most die? Key to many cancers, such as melanoma—a type of skin cancer—is the expression of a membrane receptor protein called AXL, which recognizes another abundant protein in tumors, called GAS6. The interaction between the two, GAS6 and AXL, has been shown to increase invasion and favor survival, promoting metastasis, and also contributing to cells developing resistance to therapy.

The collaboration between the research groups Diabecancer Molecular, led by Dr. Custodia García Jiménez of the Rey Juan Carlos University (URJC), and the group of Dr. Colin Goding (LICR, University of Oxford), revealed in Previous works that stress, including nutrient deprivation, triggers cancer cells to become invasive. The result of this collaboration is the new findings that reveal how invasive cells survive once outside the tumor.

Once invasive cells leave the primary tumor, how can AXL be activated in the absence of GAS6? The recent published work In the scientific journal Genes & Development, led by URJC researchers Ana Chocarro Calvo and Miguel Jociles Ortega, a study reveals that only the least differentiated melanoma cells show "hungry" behavior and induce the release of fats from neighboring cells specialized in storing fat, the adipocytes. "The released fats, among which oleic acid stands out, are captured by undifferentiated cancer cells, in which they activate the AXL receptor in the absence of its usual ligand, GAS6. In this way, the fats released by the melanoma's neighboring adipocytes promote invasion and survival, which together are necessary for the successful formation of metastases by poorly differentiated melanoma cells," explains Dr. Ana Chocarro Calvo. "If the cancer cells travel through the lymph, which has a high fat content, the survival of the cancer cells is also favored," adds Miguel Jociles Ortega.

Given the key role of AXL in a variety of cancers, the results offer an important advance in our understanding of how cancer cells successfully spread throughout the body. Furthermore, this research highlights the importance of non-genetic mechanisms in this process and suggests how obesity may play a role in cancer susceptibility.

Tasks of cancer cells to achieve expansion

Melanoma is one of the two main types of skin cancer and begins in melanocytes, skin cells responsible for pigmentation, including tanning. Like other types of cancer, melanomas contain cancer cells with distinct biological properties, such as the ability to divide, stimulating tumor growth, or invade and spread to other parts of the body. This "division of labor" among cancer cells is variable, so cancer cells go through different stages.

The incidence of skin cancer in Spain has increased 15-fold in the last 50 years. In Europe, approximately 36.000 new cases of melanoma are diagnosed each year, resulting in approximately 12.000 deaths. Spain, with approximately 2.000 new cases per year, does not have the highest incidence (perhaps due to greater awareness), but mortality is very high, with approximately 700 deaths per year.