Tumors shape their surroundings in their favor – that is known. Now researchers have come across a new trick that some types of cancer are using: the degenerate cells transfer mitochondria to the healthy connective tissue cells near them. These then begin to release growth factors and other messenger substances that support the growth of the tumor. If the researchers blocked a protein in mice that controls this mitochondria transfer, the connective tissue cells were not reprogrammed and the tumor remained smaller. Maybe a starting point for new cancer therapies could be.
Cancer cells avoid cellular control mechanisms, hide from the immune system and cause blood vessels to grow into the tumor and supply it. In addition, cancer cells also make the connective tissue cells in their surroundings, the fibroblasts, their accomplices. Even earlier studies have shown that the reprogrammed fibroblasts support the tumor in its growth, protect it from the immune system and chemotherapeutic agents and promote metastases. How exactly from healthy fibroblasts cancer is not yet fully understood.
Reprogramming according to power plant transfer
A team around Michael Cangkrama from ETH Zurich has now tracked down a trick of the tumor cells. In a cell culture with skin cancer cells and normal fibroblasts, the researching tiny tubes noticed between the two cell types. More detailed studies revealed that the tumor cells transferred some of their mitochondria to their previously healthy neighbors. Mitochondria are the cellular power plants that produce chemical energy in the form of the molecule of adenosine triphosphate (ATP). “The transfer of mitochondria from tumor cells leads to functional changes in the fibroblasts,” reports the research team.
The hijacked cells produced more ATP, increased faster and poured increased growth factors and other cellular messenger substances. In this way, they help the cancer cells to grow faster and also ensure that new blood vessels are formed in the vicinity of the tumor. This applied not only to skin cancer, but also for other types of cancer such as breast cancer and pancreatic cancer, as Cangkrama and his colleagues observed in further experiments. In their experiments, they also demonstrated that tumor -promoting changes in the fibroblasts only take place if the mitochondria actually come from cancer cells. Instead, if they transferred additional cell power plants from healthy cells to the fibroblasts, they were not reprogrammed.
Approach for new therapies?
In order to fathom the molecular mechanisms, the researchers started looking for proteins that are known to support the exchange of mitochondria between cells. They came across the protein Miro2. “This protein is produced very strongly in those cancer cells that transmit their mitochondria,” reports Cangkrama’s colleague Sabine Werner. This was not only in cell culture, but also in rehearsals of human tissue. In particular on the edges of tumors that grow into the tissue invasively, the researchers demonstrated high concentrations of Miro2 – exactly where tumor cells and fibroblasts are directly neighboring.
From the researchers’ point of view, Miro2 could be a promising starting point for new cancer therapies. If they blocked the protein in mice, the mitochondria transfer failed, the fibroblasts were not reprogrammed and the tumor could grow less. “The Miro2 blockade worked in the test tube and in the mouse model,” summarizes Werner. “It is still unexplored whether it works in human tissue.”
Source: Michael Cangkrama (ETH Zurich) et al., Nature Cancer, DOI: 10.1038/S43018-025-01038-6
