Researchers at ETH Zurich published a study in Nature Cancer showing that cancer cells exploit a mechanism meant to repair damaged cells in order to provide healthy cells with additional mitochondria and reprogram them to assist in tumor growth.
Lab at ETH Zurich. © ETH Zurich / Gian Marco Castelberg
The team found that cancer cells use tubes made of glycerophospholipids, which make up cell membranes, to connect themselves to fibroblast cells, which make up connective tissue in animals and play a critical role in wound healing. The cancerous cells transfer their mitochondria to the healthy fibroblast cell. Once the fibroblast cells have the new mitochondria, they become cancer-associated fibroblasts (CAFs). CAFs multiply faster, produce more ATP and secrete more growth factors and cytokines. Cytokines are small proteins that play an important role in immune system signaling, helping to regulate immune responses.
The researchers were able to observe the mitochondrial transfers by incubating cancer cells with MitoTracker green, which stains mitochondria in living cells. They reported that only the fibroblasts in close proximity to the cancer cells became positive for MitoTracker green after 24 hours, meaning these cells now contained the mitochondria of a cancer cell.
The tumor-associated fibroblasts alter the extracellular matrix to allow cancer cells to thrive. The researchers found that this phenomenon plays a role in breast and pancreatic cancer as well as skin cancer.
MIRO2 transfers mitochondria
The mitochondrial transfer is aided by the protein MIRO2. The researchers detected this protein in cell cultures and samples of human tissue. It was especially present in cancerous cells at the edge of a tumor, which are closer to fibroblasts.
Previous studies have shown that Miro proteins play a role in mitochondrial transfer. Miro proteins connect the outer and inner mitochondrial membranes. They are also involved in mitochondria-endoplasmic reticulum communication, Ca metabolism and recycling damaged organelles.
Inhibiting MIRO2
The researchers found that mitochondrial transfer was inhibited by blocking the formation of MIRO2. This was tested in tissue samples and mice. To test this in humans, the researchers need to find an inhibitor that will have few side effects. While this is a promising advancement in understanding tumor growth, it will likely be years before this knowledge yields a therapy that can be developed and tested.
