Updates on mechanistic insights and targeting of tumour metastasis

Abstract

Malignant tumours are one of the major diseases that seriously endanger human health. The characteristics of their invasion and metastasis are one of the main causes of death in cancer patients, and these features cannot be separated from the participation of various molecules-related cells living in the tumour microenvironment and specific structures. Tumour invasion can approximately be divided into several specific steps according to the movement of tumour cells. In each step, there are different actions in the tumour microenvironment that mediate the interactions among substances. Researchers are attempting to clarify every mechanism of the tumour dissemination. However, there is still a long way to the final determination. Here, we review these interactions in tumour invasion and metastasis at the structural, molecular and cellular levels. We also discuss the ongoing studies and the promise of targeting metastasis in tumour therapy. K E Y W O R D S metastasis, tumour invasion, tumour microenvironment | 2077 FENG Et al. How to cite this article: Feng Z, Yu Q, Zhang T, Tie W, Li J, Zhou X. Updates on mechanistic insights and targeting of tumour metastasis.

A Tale of Two Cancers: A Current Concise Overview of Breast and Prostate Cancer

“…Determining the cancer stage and codifying using a classification system is fundamental to the prognosis of PC and BC [ 104 ]. The TNM staging system (tumor-node-metastasis) is widely employed for most solid tumor progression where each letter represents various stages (T- local growth (4 stages), N- lymph node status (3 stages), and M- distant metastasis (2 stages)), for a total of 24 different TNM combinations [ 104 , 105 , 106 , 107 , 108 ]. Separating tumors into different categories with varying behavior and prognosis based on morphology was the basis of the traditional classification system [ 85 ].…”

“…However, novel procedures based on molecular methods have evolved to improve tumor classification [ 85 ]. In general, ‘histological grade’ based on tumor differentiation (tumor vs normal tissue degree of similarity) includes Grade X (unknown/undetermined grade), Grade 1 (highly differentiated), Grade 2 (medium-differentiated), Grade 3 (low-differentiated), Grade 4 (undifferentiated), plus other identifiers including lymphatic invasion (L), venous invasion (V), and residual tumor (R) [ 105 , 107 ]. The reader is directed towards other reviews [ 104 , 106 , 107 , 109 ] for further information on staging and classification of cancer.…”

Aspects fondamentaux du développement tumoral

“…La formation de métastases est un événement majeur dans l'histoire naturelle d'un cancer et a des conséquences particulièrement péjoratives sur le pronostic des patients [18,19]. Le processus métastatique comporte plusieurs étapes distinctes relativement bien caractérisées et fait intervenir de très nombreux effecteurs moléculaires [32] (Figure 5). En particulier, les cellules tumorales doivent, dans un premier temps, se détacher de la tumeur primitive et pénétrer dans la circulation sanguine ou lymphatique afin de se disséminer dans l'organisme, puis coloniser un nouvel organe et se multiplier pour donner à terme une tumeur secondaire ou métastase.…”

“…En particulier, les cellules tumorales doivent, dans un premier temps, se détacher de la tumeur primitive et pénétrer dans la circulation sanguine ou lymphatique afin de se disséminer dans l'organisme, puis coloniser un nouvel organe et se multiplier pour donner à terme une tumeur secondaire ou métastase. Chacune de ces étapes requiert l'acquisition de nouvelles propriétés biologiques: motilité cellulaire et aptitude à dégrader la matrice extra-cellulaire, résistance aux forces de cisaillement imposées par la circulation dans les fluides biologiques, échappement au système immunitaire, et surtout, capacité à survivre et à proliférer au sein d'un nouvel environnement [32]. Les mécanismes moléculaires et cellulaires à l'origine de la maladie métastatique bien que faisant l'objet d'intensives recherches sont toujours relativement mal connus à l'heure actuelle.…”

Effects of a Differentiating Therapy on Cancer-Stem-Cell-Driven Tumors

“…The cancer stem cell hypothesis states that cancer growth is driven by a subpopulation of CSCs that have the ability to self-renew and differentiate, giving rise to the DCCs that comprise the tumor bulk [1,2,3]. They can also reversibly enter quiescent states and resist radiotherapy and cytotoxic drugs, which helps to explain tumor recurrence and metastasis [4,5,6,7,2,8,9,10,11,12]. The hypothesis has been backed up by the identification of CSCs in a growing and diverse group of tumors.…”