Highly invasive placentas ca. 15 mya: metastasis, rewiring by endoviruses

The rate of cancer and cancer malignancy differ greatly among mammalian species. The placental – maternal interface is also highly variable between placental mammals. Here I want to discuss recent advances that suggest that there is a causal connection between the evolution of placental biology and the biology and rate of cancer malignancy.

Cancer is a complex disease with different stages from the origin of the primary tumor to the establishment of secondary tumors in other organs than that of its origin. In this talk I will focus on the initial stages of malignancy, i.e. after the formation of a primary tumor and before the dissemination of cancer cells through the lymph vessels. This is the process of local invasion into the tumor surrounding stroma. This stage is the one that has inspired most of the comparisons between cancer and [invasive] placentation. I will present previously published work supporting the notion that the critical cell type in this process is the tumor associated fibroblast population explaining species differences in malignancy rate among species correlated with placental phenotype. Then I will present evidence that the gene expression evolution in uterine endometrial fibroblasts and skin fibroblasts is correlated, suggesting that evolutionary change in the uterus can lead to changes in the skin fibroblasts and vice versa. I like to end with some speculations how the evolutionary biology of placental implantation may be useful for translational efforts to make cancer less malignant for humans.