Mitochondrial Haplotype of the Host Stromal Microenvironment Alters Metastasis in a Non-cell Autonomous Manner.

Autor:	Brinker AE; Department of Cancer Biology, The University of Kansas Medical Center, Kansas City, Kansas.; Department of Molecular and Integrative Physiology, The University of Kansas Medical Center, Kansas City, Kansas.; The University Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, Kansas.; Heartland Center for Mitochondrial Medicine., Vivian CJ; Department of Cancer Biology, The University of Kansas Medical Center, Kansas City, Kansas.; Heartland Center for Mitochondrial Medicine., Beadnell TC; Department of Cancer Biology, The University of Kansas Medical Center, Kansas City, Kansas.; The University Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, Kansas.; Heartland Center for Mitochondrial Medicine., Koestler DC; The University Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, Kansas.; Department of Biostatistics, The University of Kansas Medical Center, Kansas City, Kansas., Teoh ST; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan., Lunt SY; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan.; Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan., Welch DR; Department of Cancer Biology, The University of Kansas Medical Center, Kansas City, Kansas. dwelch@kumc.edu.; Department of Molecular and Integrative Physiology, The University of Kansas Medical Center, Kansas City, Kansas.; The University Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, Kansas.; Heartland Center for Mitochondrial Medicine.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2020 Mar 01; Vol. 80 (5), pp. 1118-1129. Date of Electronic Publication: 2019 Dec 17.
DOI:	10.1158/0008-5472.CAN-19-2481
Abstrakt:	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. SIGNIFICANCE: Stromal mitochondrial polymorphisms affect metastatic colonization through reactive oxygen species and mitochondrial-nuclear cross-talk. (©2019 American Association for Cancer Research.)
Databáze:	MEDLINE
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