Mapping Mitochondria's “Dance” May Be a Path to Starving NSCLC
With multiple imaging techniques and AI, scientists create 3D stories about how mitochondria fuel tumors. The sequel? How to turn off the power source.
The Challenge
By the time most people are diagnosed with non-small cell lung cancer (NSCLC), it has spread outside the lung. How long people survive depends on how far the disease has spread from its starting point. If it is caught early, about 65% of people survive at least 5 years after diagnosis. If it has spread to distant parts of the body, only about 5% of people survive at least 5 years. To improve survival for people with this most common type of lung cancer in the United States, scientists want to learn more about how NSCLC tumors develop and grow.
One area they’re looking at is mitochondria. These are the tiny “powerhouses” in all the body’s cells, extracting energy from the nutrients in the food we eat and converting it into a form of energy that cells can use. Mitochondria move around rapidly, fuse together, and break apart. They change shape depending on the kind of nutrient they intend to “eat.”
Cells that need a lot of energy, like muscle cells—and cancer cells—can contain thousands of mitochondria.
Scientists have long known that mitochondria play a crucial role in how energy is processed and produced in cancer cells. They know that mitochondria form organized structural networks that affect how much energy cancer cells can make. But few studies have looked at exactly how these networks work to create energy.
Until recently, there has not been an easy way to get clear images of mitochondrial activity in living animals. Now scientists have developed a noninvasive way to capture images of mitochondria with the use of positron emission tomography, known as PET, combined with other imaging techniques and artificial intelligence (AI). The use of these technologies is the beginning of a new focus of NSCLC research.?
The Research
绿帽社 (ACS) research grantee, David Shackelford, PhD, works with the Jonsson Comprehensive Cancer Center at UCLA in Los Angeles. The Shackelford lab studies how cellular messages and metabolism interact, especially in terms of tumor development.
Shackelford and a team of researchers recently published a study in describing how the activity of mitochondria in mice with NSCLC relates to the flow of energy (known as bioenergetic capacity) tumors need to keep growing.?
Our study describes how creating highly detailed three-dimensional (3D) maps can help us understand the cellular, structural, and functional characteristics of mitochondrial networks in lung tumors using genetically engineered mouse models of NSCLC."
PET-guided multi-modality imaging of NSCLC. Shackelford's team generated 3-dimensional (3D), high-resolution maps of the mitochondrial networks in common subtypes of NSCLC tumors. To do that, they combined these 3 technologies.
- PET (positron emission tomography) imaging allowed the team to visualize mitochondrial activity noninvasively in living mice via PET by using a tracer that they developed for imaging lung tumors. The tracer literally accumulates in the mitochondria of tumor tissue enabling them to highlight cells and tissues that use lots of energy. With PET they saw that the two subtypes of NSCLCs they were studying, adenocarcinoma and squamous cell carcinoma, have distinct ways of producing and using energy.
- Micro CT scans, like medical CT scans, use X-rays to make images, but on a much smaller scale and with clearer resolution. Shack