Evolution of placental invasion and cancer metastasis are causally linked

Kshitiz, Junaid Afzal, Jamie D. Maziarz, Archer Hamidzadeh, Cong Liang, Eric M. Erkenbrack, Hong Nam, Jan Dirk Haeger, Christiane Pfarrer, Thomas Hoang, Troy Ott, Thomas Spencer, Mihaela Pavličev, Douglas F. Antczak, Andre Levchenko, Günter P. Wagner

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1743-1753
Number of pages11
JournalNature Ecology and Evolution
Issue number12
StatePublished - Dec 1 2019

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Ecology


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