Placental invasion into the maternal endometrium of the uterus has substantial similarities with the early spread of cancer in the stroma (the part of a tissue or organ with a structural or connective role).
These similarities have inspired the hypothesis that trophoblasts (the continuous cell layer of fibroblasts that limit the egg, which became blastocyst at day 6 after fertilization) have developed the ability to invade the endometrium, leading to invasive placentation. Invasion of a specific type of trophoblast (extravillous trophoblast) in the maternal uterus is a vital step in the establishment of pregnancy.
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These mechanisms can be reactivated in cancer cells, leading to a predisposition to metastasis. It had been hypothesized (the ELI hypothesis) that cancer malignancy should be limited to placental mammals where invasive placentation first evolved. But there are several counterexamples.
In a recent article, the authors explore an alternative scenario in which stromal cells of the uterus evolved to resist or allow invasion, determining the outcome of placental invasiveness. The likelihood that changes in the stromal environment will lead to changes in cancer malignancy is reinforced by the fact that the molecular mechanisms used by cancer cells to metastasize are shared with other biological processes.
For example, mechanisms regulating gastrulation, wound healing, leukocyte extravasation, etc., are shared with both trophoblast and cancer invasion. This implies that invasive cancer cells use mechanisms that have evolved much earlier than placental invasion and, therefore, the evolution of invasive placentation per se can not be responsible for the origin of malignant cancer.
It is important to note, however, that the invasive nature of the placenta continued to evolve after its origin. Mammalian species differ in their tumorigenesis potential, as well as their vulnerability to cancer metastasis.
While the evolution resulted in an even higher degree of invasiveness in great apes, which includes humans, a complete loss of placental invasion has evolved in hoofed mammals, such as cows and horses and their parents, and these animals have lower malignancy rates for a variety of cancers.
In a recent review, Constanzo et al. presented compelling arguments for a model in which cancer progression in humans includes reactivation of the expression of embryonic genes normally controlling placental development and the development of the placenta. immune evasion.
For example, melanoma occurs in cattle and equines but remains largely benign; while it is very malign in the human. This correlates with the phenotype of the fetal-maternal interface (the degree of placental invasion during pregnancy). In particular, these results support that TGF-β secretion and high non-canonical WNT signaling in stromal cells are causal factors accounting for the high vulnerability of human stromal tissues to cancer invasion, at least in the case of melanoma .
Their data support the ELI hypothesis, suggesting that differences in stromal gene expression between species are critical in determining the degree of embryo implantation as well as stromal resistance to early cancer dissemination.
