Unconventional modes of intercellular communication can have large impacts in the context of homeostasis and disease. We have previously discovered that macrophages transfer cytoplasm to melanoma cells in vivo. Furthermore, 70% of melanoma cells that receive macrophage cytoplasm also disseminate from the primary transplantation site in vivo. These data suggest macrophages transfer a “package” of molecules that influence recipient cell behavior. However, central questions remain: 1) what is identity of the transferred molecules? and 2) how do these molecules influence cell behavior? We recently discovered that cell contact-dependent mitochondrial transfer occurs from macrophages to cancer cells. In contrast to previous held views on the mechanisms of mitochondrial transfer, our findings reveal that transferred mitochondria serve as a signaling source in the recipient cancer cell, rather than functioning as an energy-producing organelle. Our results suggest that macrophage mitochondrial transfer instruct cancer cells to become more robust and metastatic.

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