Research Assistant Professor Stony Brook University CENTERPORT, New York, United States
Disclosure(s):
Anne G. Savitt, PhD: No financial relationships to disclose
Introduction/Rationale: Tumor cells are in constant need of energy and it has been shown that mitochondrial transfer from T cells to tumor cells can provide that. Complement protein C1q is present on tumor cell surface while the receptor for its globular heads, gC1qR, is present both on the surface and within the mitochondria of T cells.
Methods: The aim of the present study was therefore to investigate whether the interaction between gC1qR on T cells and C1q on the tumor cell facilitates hijacking of T cell mitochondria, resulting in T cell exhaustion. To this end, breast cancer cell lines SKBR3, MDA-MB-231, and MDA-MB-468 were treated with ethidium bromide (EtBr) to remove mitochondria, adding uridine (uri) as an alternate energy source. Conditions examined were: untreated, EtBr no uri, EtBr low uri, and EtBr high uri. At timepoints, tumor cell mitochondria were stained with fluorescent mitochondrial dye MitoRed and examined by fluorescence microscopy.
Results: By day five, untreated tumor cells exhibited increased fluorescence while cells treated with EtBr showed a decrease. Once mitochondria were depleted, MOLT4 T cells were stained with MitoRed and co-cultured with unstained tumor cells. On day 13, tumor cells co-cultured with MitoRed-stained T cells showed fluorescence in both tumor and T cells.
Conclusion: Fluorescence in tumor cells was attributed to T cell mitochondrial taken up by tumor cells, confirming the transfer of mitochondria from T cells to tumor cells. Future studies will examine the roles of C1q and gC1qR in mitochondrial transfer.
