Review: Tumour progression and metastasis (inflammation, tumor latency...)

open access

Abstract

Introduction

Components of the pre-metastastic niche

Types of cells

Tumour-associated macrophages (TAM)

Cancer-associated fibroblasts (CAF)

Pericytes

The composition of an inflammatory environment

The epithelial–mesenchymal transition

Transcriptional regulation of the epithelial–mesenchymal transition

Signalling pathways that activate the epithelial transition

The metalloproteinases

The metalloproteinases and the progression of cancer

Angiogenesis

Tumour latency and progression

Stroma and growth of the tumour cells: pre-clinical studies

Conclusion

Cancer is not only the transformation of individual cells into a state of cellular proliferation, but a disruption of the forms in which the tissues regulate their processes and affect the systemic interactions with the affected organism. Currently, the fundamental treatments against cancer continue to be surgery, radiation therapy, and chemotherapy, which usually destroys the primary tumour, but whose action is very limited against metastasis. This is why it is necessary to continue investigating to find new prognostic markers and new therapeutic targets for metastasis before it occurs, as the early detection of these markers could determine which cases require treatment and avoid it in those patients without a risk of metastasis. Thus, for example, the monitoring of growth factors and cytokines in the blood which may induce the formation of the premetastatic niche would be fundamental. At the same time, determining the blood levels of components of the metastatic niche such as the VEGFR1 protein circulating or interfering with the formation of inflammatory components such as type CD11b myeloid cells is indispensable for this purpose.

Genetic, cellular biology, and molecular studies, as well as those of the internal and external environmental contexts, indicate that tumour growth is not only determined by its cells, but also by the tumour microenvironment and the entire context in which the organism functions. In this way, the progression of cancer is the result of a very complex relationship between the different malignant and non-malignant cell types, components of the stroma, and the entire body of the organism.

Due to the implication of metastasis in mortality due to cancer, it is also necessary to search for new ways to integrate the two focuses which dominate the current science: the reductionist vision and the systemic vision sustained by the science of complexity.