Oncofetal reprogramming in tumour development and progression

Abstract

Embryonic development is characterized by rapidly dividing cells, cellular plasticity and a highly vascular microenvironment. These features are similar to those of tumour tissue, in that malignant cells are characterized by their ability to proliferate and exhibit cellular plasticity. The tumour microenvironment also often includes immunosuppressive features. Reciprocal communication between various cellular subpopulations enables fetal and tumour tissues to proliferate, migrate and escape immune responses. Fetal-like reprogramming has been demonstrated in the tumour microenvironment, indicating extraordinary cellular plasticity and bringing an additional layer of cellular heterogeneity. More importantly, some of these features are also present during inflammation. This Perspective discusses the similarity between embryogenesis, inflammation and tumorigenesis, and describes the mechanisms of oncofetal reprogramming that enable tumour cells to escape from immune responses, promoting tumour growth and metastasis. Malignant cells show uninhibited proliferation and cellular plasticity, features also reminiscent of embryogenesis. In this Perspective, Sharma and colleagues present their oncofetal ecosystem concept, discuss evidence of oncofetal reprogramming in malignant and non-malignant cells, and debate the therapeutic relevance of these findings.