Redeployment of Placental Gene Programming: Can Invasive Placentation Molecular Switches Complement the Hallmarks of Cancer?

Abstract

Placentation arose in mammalian evolution some 150-200 M years ago and integrates in a rather ingenious manner a large number of previously evolved multicellular regulatory pathways which include: angiogenesis, inflammatory cytokines and interleukins, HLA expression, immune peptides, immune regulatory receptors (for NK decidual cells, T and B cells, including Tregs, macrophages, antigen-presenting cells ), endothelial cells and fibroblasts, immune checkpoints (including PD-L1), many paracrine or endocrine hormones and growth factors, tissue enzymes, extracellular vesicles, several different mechanisms for epithelial-mesenchymal transitions, several hypoxia adaptations, morphogenetic changes, and others. Speculating from real genomics and epigenetic data from a single clinical case of a pregnant young woman with breast cancer, it has been recently proposed that mammalian cancer cells do not have to invent “de novo” immune escape mechanisms, including so-called “immune editing”, but to redeploy–probably by epigenetic mechanisms–intrinsic or encrypted gene programmes physiologically used by the process of invasive placentation in mammals. Most of these programmes were not evolved specifically for the placenta–but there were probably some exceptions, such as those still poorly understood key pathways related to foeto-maternal tolerance or perhaps trophoblast differentiation and decidual invasion. In my opinion, invasive placentation molecular switches can complement the hallmarks of cancer, by re-using “placental gene programming” to the competitive advantage of cancer cells.