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Nat Ecol Evol. 2019 Dec;3(12):1743-1753. doi: 10.1038/s41559-019-1046-4. Epub 2019 Nov 25.

Evolution of placental invasion and cancer metastasis are causally linked.

Author information

1
Yale Institute of Systems Biology, Yale University, West Haven, CT, USA. kshitiz@uchc.edu.
2
Department of Biomedical Engineering, Yale University, New Haven, CT, USA. kshitiz@uchc.edu.
3
Department of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT, USA. kshitiz@uchc.edu.
4
Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
5
Yale Institute of Systems Biology, Yale University, West Haven, CT, USA.
6
Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT, USA.
7
Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
8
Center for BioMicrosystems, Korea Institute of Science and Technology, Seoul, South Korea.
9
Institute of Anatomy, University of Veterinary Medicine, Hannover, Germany.
10
Department of Animal Science, Center for Reproductive Biology and Health, Penn State University, University Park, PA, USA.
11
Division of Animal Sciences, University of Missouri, Columbia, MO, USA.
12
Cincinnati Children's Hospital and Medical Center, Cincinnati, OH, USA.
13
Baker Institue for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
14
Yale Institute of Systems Biology, Yale University, West Haven, CT, USA. andre.levchenko@yale.edu.
15
Department of Biomedical Engineering, Yale University, New Haven, CT, USA. andre.levchenko@yale.edu.
16
Yale Institute of Systems Biology, Yale University, West Haven, CT, USA. gunter.wagner@yale.edu.
17
Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT, USA. gunter.wagner@yale.edu.
18
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale Medical School, New Haven, CT, USA. gunter.wagner@yale.edu.
19
Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA. gunter.wagner@yale.edu.

Abstract

Among mammals, placental invasion is correlated with vulnerability to malignancy. Animals with more invasive placentation (for example, humans) are more vulnerable to malignancy. To explain this correlation, we propose the hypothesis of 'Evolved Levels of Invasibility' proposing that the evolution of invasibility of stromal tissue affects both placental and cancer invasion. We provide evidence for this using an in vitro model. We find that bovine endometrial and skin fibroblasts are more resistant to invasion than are their human counterparts. Gene expression profiling identified genes with high expression in human but not in bovine fibroblasts. Knocking down a subset of them in human fibroblasts leads to stronger resistance to cancer cell invasion. Identifying the evolutionary determinants of stromal invasibility can provide important insights to develop rational antimetastatic therapeutics.

PMID:
31768023
DOI:
10.1038/s41559-019-1046-4

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