Cancer metastasis as a non-healing wound

Abstract

AbstractMost cancer deaths are caused by metastasis: recurrence of disease by disseminated tumour cells at sites distant from the primary tumour. Large numbers of disseminated tumour cells are released from the primary tumour, even during the early stages of tumour growth. However, only a minority survive as potential seeds for future metastatic outgrowths. These cells must adapt to a relatively inhospitable microenvironment, evade immune surveillance and progress from the micro- to macro-metastatic stage to generate a secondary tumour. A pervasive driver of this transition is chronic inflammatory signalling emanating from tumour cells themselves. These signals can promote migration and engagement of stem and progenitor cell function, events that are also central to a wound healing response. In this review, we revisit the concept of cancer as a non-healing wound, first introduced by Virchow in the 19th century, with a new tumour cell-intrinsic perspective on inflammation and focus on metastasis. Cellular responses to inflammation in both wound healing and metastasis are tightly regulated by crosstalk with the surrounding microenvironment. Targeting or restoring canonical responses to inflammation could represent a novel strategy to prevent the lethal spread of cancer.