9.1 Introduction to Metastasis

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What is Metastasis?


Metastasis is the process of cancer cell dissemination and colonization to distant sites in the body. It is responsible for as much as 90% of cancer related deaths (1). Establishment of pro-metastatic phenotypes is the first step in escaping the primary tumor and invading other tissues in the body to form secondary tumors. Widely recognized pro-metastatic cell phenotypes include increased proliferation, mobility, invasion, resistance to apoptosis, and ability to induce angiogenesis (2). Invasion is described as the movement through the extracellular matrix (ECM) and basement membrane. Angiogenesis is the process through which new blood vessels develop.


In a healthy state, epithelial cells are bound to the basement membrane and to each other by cell-ECM and cell-cell junctions, respectively. Thus, normal epithelial cells exist primarily in a stationary state. Yet the majority of life-threatening metastasizing carcinoma tumors originate from cells that have undergone a transition to become independent, migratory mesenchymal cells, also known as invasive cancer cells (3). This transition, referred to as the epithelial-to-mesenchymal transition (EMT), is the process in which epithelial cells overcome the limitations of these junctions and acquire the ability to move through the ECM and invade localized blood vessels (1). Once in the blood stream, the cancer cells must then resist apoptosis and survive long enough to invade a different, often distant, site in the body where a secondary tumor can be established. In this chapter, the key steps in the processes of the metastatic invasion cascade will be discussed in the general order which they occur in cancer metastasis, as summarized in Figure 12.1.1. Accordingly, the following sections will present the current knowledge regarding each step and highlight potential therapeutic strategies.


Figure 9.1.1 The metastatic cascade. Released under the Creative Commons Attribution-ShareAlike 4.0 International license (CC BY-SA 4.0).



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