Abstract
Metastasis, a leading contributor to the morbidity of cancer patients, occurs through a multi-step process: invasion, intravasation, extravasation, colonization, and metastatic tumor formation. Each process is not only promoted by cancer cells themselves but is also affected by their microenvironment. Given this complexity, drug discovery for anti-metastatic drugs must consider the interaction between cancer cells and their microenvironments. The zebrafish is a suitable vertebrate animal model for in vivo high-throughput screening studies with physiological relevance to humans. This review covers the zebrafish model used to identify anti-metastatic drugs.
Highlights
Overt metastases, the end result of malignant alteration in cancer cells, are responsible for approximately 90% of cancer-associated mortality
Metastasis consists of a multi-step process: invasion in which neoplastic epithelial cells invade into the adjacent tissue after they lose cell-cell adhesion; intravasation in which tumor cells penetrate through the endothelium of blood or lymphatic vessels to enter the systemic circulation; survival in the circulatory system in which certain circulating tumor cells appear able to survive in the bloodstream; extravasation in which cancer cells extravasate through the capillary endothelium at distal sites; colonization in which cancer cells proliferate in a new environment, and metastatic tumor formation in which cancer cells form a new tumor in secondary organs (Figure 1) [1,2,3]
From the therapeutic point of view, the metastatic process can be divided into two phases: the early phase including tumor cell invasion and extravasation, and the late phase consisting of colonization and metastatic tumor formation
Summary
The end result of malignant alteration in cancer cells, are responsible for approximately 90% of cancer-associated mortality. The interaction between cancer cells with their microenvironments must be considered while developing therapeutic strategies for metastasis. From the therapeutic point of view, the metastatic process can be divided into two phases: the early phase including tumor cell invasion and extravasation, and the late phase consisting of colonization and metastatic tumor formation. During the former phase, anti-metastatic treatments focus on inhibiting the spread of cancer cells to distant organs. The goal of treatment during the latter phase is to inhibit the proliferation of disseminated cancer cells in distant organs [6].
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