Hypoxia induces core-to-edge transition of progressive tumoral cells: A critical review on differential yet corroborative roles for HIF-1α and HIF-2α

Abstract

There is a dynamic heterogeneous cellularity dispersing within the edge and core of tumor. This heterogeneity is predominantly for developing adaptive mechanisms as a response to various harm situations. Edge cells are more quiescent, invasive and resistant than cells seeded in the core. Higher proliferation and thus more cellular density is a significant characteristic of core cells. An increase in the number of resistant cells in higher stage cancers is a predictable phenomenon, which is partly due to core-to-edge cellular transitioning, and thus expanding the edge area of tumor. The question here is that what differences are in the tumor infrastructure causing these variations and how it can be related to therapy? Here, we have a special focus over hypoxia as a dominant contributing factor for this cellular dispersing, challenging views toward this context and push them to our direction. It would be fair to announce that combine targeting for both hypoxia inducible factor (HIF)-1α and HIF-2α may hold a therapeutic promise for high-stage tumors, but an ongoing research is required to direct this hypothesis toward certainty.

Keywords: Angiogenesis; Core; Edge; Hypoxia inducible factor (HIF); Resistance; Tumor stage.