Mitochondrial Haplotype of the Host Stromal Microenvironment Alters Metastasis in a Non-cell Autonomous Manner
Copyright policy )Mitochondrial Haplotype of the Host Stromal Microenvironment Alters Metastasis in a Non-cell Autonomous Manner
AbstractMitochondria 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.Significance:Stromal mitochondrial polymorphisms affect metastatic colonization through reactive oxygen species and mitochondrial–nuclear cross-talk.
- University of Kansas Medical Center United States
- UNIVERSITY OF KANSAS MEDICAL CENTER
- University of Kansas United States
- Michigan State University United States
- University of Kansas Cancer Center United States
Cell Nucleus, Male, Lung Neoplasms, Carcinogenesis, Breast Neoplasms, Mice, Inbred Strains, DNA, Mitochondrial, Polymorphism, Single Nucleotide, Mitochondria, Disease Models, Animal, Mice, Haplotypes, Superoxides, Cell Line, Tumor, Tumor Microenvironment, Animals, Humans, Female, Neoplasm Metastasis, Signal Transduction
Cell Nucleus, Male, Lung Neoplasms, Carcinogenesis, Breast Neoplasms, Mice, Inbred Strains, DNA, Mitochondrial, Polymorphism, Single Nucleotide, Mitochondria, Disease Models, Animal, Mice, Haplotypes, Superoxides, Cell Line, Tumor, Tumor Microenvironment, Animals, Humans, Female, Neoplasm Metastasis, Signal Transduction
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).15 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!