Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Transplanting Heterologous Mitochondria from Human Umbilical Vein Endothelial Cells Reduces the Malignancy of Melanoma Cells

Fu-Chen Kuo
,
Bi-Ling Cheng
,
Ching-Chung Tsai
ORCID logo ,
Ping-Chen Chen
,
Hsin-Yi Tsai
,
Kuen-Jang Tsai
,
Yaw-Bin Huang
ORCID logo ,
Chung-Jung Liu
,
Deng-Chyang Wu
,
Ming-Wei Lin
* ORCID logo ,
Bin Huang
*
Version 1 : Received: 17 April 2023 / Approved: 18 April 2023 / Online: 18 April 2023 (04:10:03 CEST)

How to cite: Kuo, F.; Cheng, B.; Tsai, C.; Chen, P.; Tsai, H.; Tsai, K.; Huang, Y.; Liu, C.; Wu, D.; Lin, M.; Huang, B. Transplanting Heterologous Mitochondria from Human Umbilical Vein Endothelial Cells Reduces the Malignancy of Melanoma Cells. Preprints 2023, 2023040477. https://doi.org/10.20944/preprints202304.0477.v1 Kuo, F.; Cheng, B.; Tsai, C.; Chen, P.; Tsai, H.; Tsai, K.; Huang, Y.; Liu, C.; Wu, D.; Lin, M.; Huang, B. Transplanting Heterologous Mitochondria from Human Umbilical Vein Endothelial Cells Reduces the Malignancy of Melanoma Cells. Preprints 2023, 2023040477. https://doi.org/10.20944/preprints202304.0477.v1

Abstract

The development of using mitochondrial transplantation in medical therapy are currently discussed. According to the endosymbiotic theory, the movement of mitochondria between different cells is possible. Therefore, an idea of transferring the mitochondria purified from the cells with a limited lifespan to shorten the lifespan of immortal cancer cells was generated. Human umbilical vein endothelial cell (HUVEC) is a kind of primary cell with a limited lifespan. In the present study, the mitochondria purified from HUVEC were applied to alter the malignance of B16F10 melanoma cell. In the comparison of the basic function of mitochondria, HUVEC mitochondria exhibited a higher mitochondrial membrane potential (MMP), while the lower levels in ATP, mitochondrial DNA (mt-DNA) and mitochondrial protein (mt-protein) as compared to melanoma B16F10. After transplanted the B16F10 with HUVEC mitochondria, the migration, invasion, and the proteins involved in cancer stemness were decreased, however, the proteins involved in cell proliferation, such as cyclin D1 and cyclin E1 were increased. In addition, the levels of ATP, mt-DNA and mt-protein of B16F10 were also reduced. As for the dynamics of mitochondria, the reduced expressions of DRP1 and LC3 II revealed that transferred mitochondria can attenuate the mitophagy of B16F10. In mice, inoculated the B16F10 carrying the transplanted HUVEC mitochondria resulted in the larger size of tumor, which is corresponded to the higher levels of cyclin D1 and E1. Interestingly, the lower expressions of N-cadherin, α-SMA and MMP-9 reveled the tumor were decreased in mesenchymal characteristics. Therefore, despite the HUVEC mitochondria did not inhibit the proliferation of B16F10, the metastatic characteristic was reduced.

Keywords

Mitochondrial transplantation; Mitophagy; HUVEC; melanoma; EMT; malignancy

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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