Environmental Conditions Shared by the Placenta, Cancer and COVID

During early placentation the invading trophoblastic cells are exposed to severe hypoxic conditions. Hypoxia is also well-documented in tumors and occurs to varying degrees both spatially and temporally during tumorigenesis. The implications of hypoxic conditions are not fully understood. However, it has been shown that exposure to hypoxia can increase the rate of cell division in order to seek out an oxygen supply. Hypoxia can also induce hypomethylation in cancer cells, however the extent to which this occurs is unknown. The hypoxia inducible factor (HIF) is known to be expressed in both placental and tumor cells in response to low oxygen levels. HIF expression has downstream effects on a number of different pathways including metabolism, angiogenesis and immune modulation. Notably, temporal expression of PDL-1 in invading trophoblast cells has been linked to oxygen availability. HIF knockout mice demonstrate embryonic lethality owing to abnormal placentation. HIF dysregulation has also been observed in a number of cancers. A recent review by Macklin et al. highlights the similarities between the placental and cancer microenvironments, and discusses hypoxia and subsequent HIF expression as a potential link between some of the shared functions carried out by both tissues.

The term used is onco-exaptation. The 'exaptation,' an LTR promoter, provides the means with which an otherwise fate-restricted proto-oncogene may be accessed. In otherwords, it had NOT been activated during early development. It has been awakened by the spike's literal carnival of transposon activity.