# Mitochondrial lateral transfer during metastasis

> **NIH NIH R37** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $44,879

## Abstract

Project Summary
Macrophages play paradoxical roles in cancer: They can be tumoricidal, but in many cancers, macrophages
promote metastasis. There has been growing evidence that macrophages can modulate cell behavior via
unconventional cell contact-mediated communication in development and homeostasis. We have recently
extended these paradigms by discovering that macrophages can also engage in unconventional cell contact-
mediated communication with tumor cells within the tumor microenvironment, and that these interactions
contribute to metastasis. By visualizing and manipulating highly migratory melanoma cells and their
microenvironment in vivo, we unexpectedly found that tumor-associated macrophages transfer cytoplasmic
contents to melanoma cells in a cell contact-dependent manner. Remarkably, 70-80% of melanoma cells that
received macrophage cytoplasm disseminated from the primary tumor in both zebrafish and murine models.
We are now ideally positioned to identify key component(s) that are transferred from macrophages to tumor
cells for metastasis, and how this transfer occurs. Mitochondria are dynamic organelles that perform a variety
of essential cellular functions. Mitochondria have been shown to transfer to tumor cells in vivo, restoring their
respiration and ability to form tumors. While these elegant “proof of principle” studies demonstrated that
mitochondrial lateral transfer can occur in the tumor microenvironment, the donor stromal cell(s) were not
identified, the transfer mechanism was not defined, and the fates and functions of mitochondria in tumor cells
were not characterized. Excitingly, we have found that primary human macrophages can transfer mitochondria
to human breast cancer cells and melanoma cells, two cancers in which macrophages have been shown to
play a pro-tumorigenic role. Tumor cells that receive macrophage mitochondria either by spontaneous
mitochondrial transfer in coculture, or by direct injection of purified macrophage mitochondria, exhibit increased
proliferation. Surprisingly, we find that after mitochondrial transfer occurs, the transferred mitochondria remain
as a spatially distinct population from the host mitochondrial network. Furthermore, we found that high levels of
local reactive oxygen species accumulate at transferred mitochondria, suggesting an intriguing hypothesis that
transferred mitochondria may provide a signal to tumor cells, rather than providing excess mitochondrial
function as has been previously described. To test this hypothesis, we propose to: (Aim 1) Understand how
mitochondria dynamically reorganize for mitochondrial transfer to tumor cells and (Aim 2) Determine how
mitochondrial transfer mechanistically induces cancer cell proliferation. Taken together, these experiments will
reveal whether macrophage mitochondrial transfer can instruct breast cancer and melanoma cells to become
more robust and metastatic. Our goals are to define how immune cells function in the tumor microenvironment,
...

## Key facts

- **NIH application ID:** 10816729
- **Project number:** 3R37CA247994-04S1
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Minna Roh
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $44,879
- **Award type:** 3
- **Project period:** 2021-07-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10816729

## Citation

> US National Institutes of Health, RePORTER application 10816729, Mitochondrial lateral transfer during metastasis (3R37CA247994-04S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10816729. Licensed CC0.

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