Tumour progression and metastasis

Abstract

The two biological mechanisms that determine types of malignancy are infiltration and metastasis, for which tumour microenvironment plays a key role in developing and establishing the morphology, growth and invasiveness of a malignancy. The microenvironment is formed by complex tissue containing the extracellular matrix, tumour and non-tumour cells, a signalling network of cytokines, chemokines, growth factors, and proteases that control autocrine and paracrine communication among individual cells, facilitating tumour progression. During the development of the primary tumour, the tumour stroma and continuous genetic changes within the cells makes it possible for them to migrate, having to count on a pre-metastatic niche receptor that allows the tumour's survival and distant growth. These niches are induced by factors produced by the primary tumour; if it is eradicated, the active niches become responsible for activating the latent disseminated cells. Due to the importance of these mechanisms, the strategies that develop tumour cells during tumour progression and the way in which the microenvironment influences the formation of metastasis are reviewed. It also suggests that the metastatic niche can be an ideal target for new treatments that make controlling metastasis possible.

Keywords: cancer; epithelial–mesenchymal transition; infiltration; latency; metastasis; metastatic niche; microenvironment.

Figure 1.. The sequential steps in the pathogenesis of metastasis are shown in the figure above, where each step is regulated by transitory and permanent changes in the DNA, the RNA, or by proteins. Also, most tumor cells fail to complete all of the steps, and the ‘few’ cells with metastatic ability ‘defeat’ the multiple mechanisms which impedes the formation of metastasis.

Figure 2.. In metastatic progression, time and the failure factors indicated in the figure above, play a crucial role in the prognosis and treatment of the patient with cancer, as shown in the model of the linear progression of a tumor. In time, the cells increase in malignancy. Thus the concept of ‘metastasis of metastasis’ is used in reference to the metastasis becoming in the course of time more malignant, resulting in the death of the patient, as the illness cannot be controlled.