Mitochondrial Haplotype of the Host Stromal Microenvironment Alters Metastasis in a Non-cell Autonomous Manner
Abstract
Mitochondria contribute to tumor growth through multiple metabolic pathways, regulation of extracellular pH, calcium signaling, and apoptosis. Using the Mitochondrial Nuclear Exchange (MNX) mouse models, which pair nuclear genomes with different mitochondrial genomes, we previously showed that mitochondrial SNPs regulate mammary carcinoma tumorigenicity and metastatic potential in genetic crosses. Here, we tested the hypothesis that polymorphisms in stroma significantly affect tumorigenicity and experimental lung metastasis. Using syngeneic cancer cells (EO771 mammary carcinoma and B16-F10 melanoma cells) injected into wild-type and MNX mice (i.e., same nuclear DNA but different mitochondrial DNA), we showed mt-SNP–dependent increases (C3H/HeN) or decreases (C57BL/6J) in experimental metastasis. Superoxide scavenging reduced experimental metastasis. In addition, expression of lung nuclear-encoded genes changed specifically with mt-SNP. Thus, mitochondrial–nuclear cross-talk alters nuclear-encoded signaling pathways that mediate metastasis via both intrinsic and extrinsic mechanisms.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 01, 2020
- Source ID
- 10.1158/0008-5472.can-19-2481
Entities
People
- Amanda Brinker
- Carolyn J. Vivian
- Danny R. Welch
- Devin C Koestler
- Shao Thing Teoh
- Sophia Y Lunt
- Thomas C. Beadnell
Organizations
- American Association for Cancer Research
- Congressionally Directed Medical Research Programs
- Kansas Bioscience Authority
- Michigan State University
- National Cancer Institute
- National Foundation for Cancer Research
- Susan G. Komen for the Cure
- University of Kansas Medical Center