International Business Department           Liu Bojia           January 24, 2023

  Being a picky eater is a pet peeve that many people have at one time or another, but for tumours, being a picky eater is a non-issue. Quite the contrary, tumours are more like voracious black holes, coming for any molecule that promotes their growth. We might think that since sugar is the preferred energy for cell growth, cancer cells would only choose to "eat" sugar.

  In the early stages of cancer cell growth, glucose is indeed the best choice. However, as the tumour grows in size and its vascular system becomes insufficient to support the large energy supply, the tumour becomes glucose deprived. Some studies have found that cancer cells meet their growth needs by taking in surrounding amino acids and fatty acids.

  But what if these molecules are not accessible? That's not at all difficult for cancer cells either! According to a new study by PLoS Biology, breast cancer cells consume the surrounding matrix in the absence of nutrients. These extracellular matrices (ECM) are mainly complex networks of macromolecules made up of collagen, proteoglycans, aminoglycans, etc., which are the bed for the survival of many cells. At the same time, the ECM provides structural and mechanical force support to tissues and interacts with cells.

  Some studies have observed that pancreatic cancer cells choose to take up collagen from extracellular sources as a supplement under extreme conditions, and it just so happens that ECM possesses this component. To more clearly confirm the link between cancer cell metabolism and ECM, the new study cultured breast cancer cells in collagen-containing, substrate-containing, or normal conditions, respectively, while they deprived them of amino acids favoured for growth in some of the cancer cell culture conditions.

  After a period of time, the cancer cells in the normal culture conditions and deprived of amino acids became very poorly grown and lost their usual rapid expansion and arrogance. But cancer cells with collagen or matrix, even if lacking amino acids, had a higher growth rate and a higher total number of cancer cells.

  Under the same experimental conditions, the authors also tested what healthy breast cells, and breast cancer cells at different stages, would do in response, respectively. The results show that in a state of nutrient deprivation, healthy cells and early stage breast cancer cells rarely choose to phagocytose the surrounding ECM, and only breast cancer cells that have developed metastases exhibit this type of behaviour, which suggests that this ECM phagocytosis is only gradually acquired as the tumour continues to develop.

  In turn, components of these ECM will enter the interior of the cancer cell through the process of macropinocytosis, and eventually these components will be transferred to the lysosomes for decomposition. Subsequently, the cancer cells use the energy gained from the metabolism of tyrosine and phenylalanine broken down therein to continue to survive. If the cross-linked structure of the ECM is artificially disrupted, the cancer cells will not be able to process and absorb them.

  These results also gave the authors two new insights into cancer treatment; the first strategy is to shut down the macropinocytosis process in cancer cells, and the second is to stop the metabolic recycling of the two amino acids; the authors tried to block key molecules of both processes in cellular experiments, and both turned out to be able to reduce the migration and invasive ability of breast cancer cells.

  The authors point out that the new study once again reveals the secret of accelerated tumour growth in the face of nutritional deficiencies, and targeting this key metabolic process may help treat advanced or metastatic tumours in the future.