Tumors Use Mitochondrial Transfer to Influence Surrounding Cells, Study

Researchers at ETH Zurich have uncovered a novel way that certain tumors support their survival and growth. Their study, published in Nature Cancer, demonstrates that skin cancer cells transfer mitochondria—the energy-generating compartments within cells—to nearby healthy connective tissue cells known as fibroblasts. This transfer occurs through tiny membrane-based tubes connecting the two cell types, resembling a pneumatic tube system.

This mitochondrial transfer causes a functional reprogramming of the fibroblasts into tumor-associated fibroblasts. These specialized fibroblasts multiply faster, produce more ATP (the cell’s energy molecule), and secrete increased amounts of growth factors and cytokines. These changes benefit the tumor by promoting faster cancer cell multiplication and increased tumor aggressiveness. Additionally, the altered fibroblasts modify the extracellular matrix—the structural network surrounding cells—by producing more matrix components that create an environment conducive to cancer growth. The extracellular matrix is essential for tissue stability, cell communication, and processes such as wound healing.

The discovery originated by chance when Michael Cangkrama, a former postdoctoral researcher working in Sabine Werner group, observed the nanotube-like connections in co-cultures of skin cancer cells and fibroblasts. While mitochondrial exchange between cells is known—for example, in nerve tissue after stroke to support damaged cells—it was previously unclear whether cancer cells could transfer mitochondria to fibroblasts. This research shows that cancer cells exploit a natural injury-repair mechanism to promote tumor development. Prior research had demonstrated mitochondrial transfer from fibroblasts to cancer cells, but this study reveals the process also works in the reverse direction.

Further investigations in collaboration with other ETH Zurich groups found evidence of this mitochondrial transfer in breast and pancreatic cancers, the latter being notable for its abundant fibroblasts and extensive connective tissue.

At the molecular level, the protein MIRO2 was identified as a crucial factor facilitating mitochondrial transfer. MIRO2 is produced in high quantities by cancer cells engaged in mitochondrial transfer and was detected prominently in invasive tumor regions near fibroblasts. When MIRO2 production was blocked, mitochondrial transfer was inhibited, preventing fibroblasts from converting into tumor-promoting cells. This effect was observed both in vitro and in mouse models.

Although these findings suggest targeting MIRO2 could halt tumor progression, clinical application requires development of safe MIRO2 inhibitors and extensive testing. Werner notes that translating this approach into human therapies will likely take years, but the results provide a promising foundation for future interventions.