Scientists have extended recognized that mitochondria, the “powerhouses” of cells, play a critical part in the metabolism and power production of cancer cells. Having said that, till now, tiny was recognized about the connection in between the structural organization of mitochondrial networks and their functional bioenergetic activity at the level of complete tumors.
In a new study, published in Nature, researchers from the UCLA Jonsson Complete Cancer Center applied positron emission tomography (PET) in mixture with electron microscopy to produce three-dimensional ultra-resolution maps of mitochondrial networks in lung tumors of genetically engineered mice. They categorized the tumors primarily based on mitochondrial activity and other components making use of an artificial intelligence method known as deep understanding, quantifying the mitochondrial architecture across hundreds of cells and thousands of mitochondria all through the tumor.
The authors examined two primary subtypes of non-tiny cell lung cancer (NSCLC) — adenocarcinomas and squamous-cell carcinomas and identified distinct subpopulations of mitochondrial networks inside these tumors. Importantly, they found that the mitochondria often organize themselves with organelles such as lipid droplets to produce exclusive subcellular structures that help tumor cell metabolism and mitochondrial activity.
The study was led by Mingqi Han, Ph.D., a post-doctoral researcher in the lab of David Shackelford, Ph.D. Dr. Shackelford is a UCLA Jonsson Complete Cancer Center member and Associate Professor of Pulmonary and Vital Care Medicine at the UCLA David Geffen College of Medicine.
The authors anticipate that mitochondrial populations in human cancer samples will not be mutually exclusive to their respective tumor subtype, but rather there will be a spectrum of activity.
The investigators say these findings present crucial info about the function of mitochondria in cancer cells and could lead to new approaches to cancer therapy.
“Our study represents a very first step towards creating very detailed three-dimensional maps of lung tumors making use of genetically engineered mouse models,” mentioned Dr. Shackelford. “Applying these maps, we have begun to produce a structural and functional atlas of lung tumors, which has offered us worthwhile insight into how tumor cells structurally organize their cellular architecture in response to the higher metabolic demands of tumor development. Our findings hold guarantee to inform and increase existing therapy methods when illuminating new directions from which to target lung cancer.”
“Our study has uncovered a novel acquiring in the metabolic flux of lung tumors, revealing that their nutrient preference may well be determined by the compartmentalization of their mitochondria with other organelles, either relying on glucose (“sugar”) or totally free fatty acids (“fat”),” mentioned Dr. Han. “This discovery has significant implications for creating successful anti-cancer therapies that target tumor-distinct nutrient preferences. Our multi-modality imaging method has enabled us to uncover this previously unknown aspect of cancer metabolism, and we think that it can be applied to other sorts of cancer, paving the way for additional study in this region.”