The Amazing Power of Cancer Cells to Recapitulate Extraembryonic Functions: The Cuckoo's Tricks

Abstract

Inflammation is implicated in tumor development, invasion, and metastasis. Hence, it has been suggested that common cellular and molecular mechanisms are activated in wound repair and in cancer development. In addition, it has been previously proposed that the inflammatory response, which is associated with the wound healing process, could recapitulate ontogeny through the reexpression of the extraembryonic, that is, amniotic and vitelline, functions in the interstitial space of the injured tissue. If so, the use of inflammation by the cancer-initiating cell can also be supported in the ability to reacquire extraembryonic functional axes for tumor development, invasion, and metastasis. Thus, the diverse components of the tumor microenvironment could represent the overlapping reexpression of amniotic and vitelline functions. These functions would favor a gastrulation-like process, that is, the creation of a reactive stroma in which fibrogenesis and angiogenesis stand out.

Figure 1

Representative drawing of the early mammalian embryo during gastrulation. The internalization of the extraembryonic mesoderm (EM) during gastrulation allows for the creation of the intraembryonic mesoderm (IM) that could thus join functional amniotic and vitelline properties from the amnion (A) and yolk sac (YS), respectively. BI: blood islands; C: chorionic vellosities.

Figure 2

Evolutive phases of the inflammatory cancer cell. Cancer cells can adopt an inflammatory phenotype to invade neighboring tissues and survive in these ectopic sites. In the successive phases of tumorigenesis, the cancer cells invade the host by expressing natural and adaptive immune-related mechanisms. sc: stem cell; scc: stem cancer cell; shc: stem hematopoietic cell; f: fibroblast; mn: monocyte; mf: myofibroblast; g: granulocyte; mØ: macrophage; lc: lymphatic capillary; cc: cancer cell; lnm: lymph node metastasis; hev: high endothelial venule; l: lymphocytes; pcv: postcapillary venule; bc: blood capillary; p: pericyte; *tumoral antigen.

Figure 3

Successive and overlapped stages of tumorigenesis. Genetic and epigenetic factors stimulate the formation of a cancer stem cell that invades the interstitial space favored by the inflammatory interstitial-lymphatic axis, which stands out the tissue circulation of fluid and the cellular migration. The tumor cell, by means of using the natural and adaptive immune mechanisms, becomes immunotolerant, which favors the following phases of tumor development. Then, the cancer cell induces the creation of a stroma formed by a special type of granulation tissue, and this allows for the creation of a tumoral parenchyma provided with functional heterogeneity. Finally, this heterogeneous tumor mass plunders the trophic stores of the host inducing cachexia.