Metastasis is a common cause of death in patients with solid tumors. Research in this area may lead to better identification of patients at risk of developing metastasis in addition to improved therapies for patients with metastatic disease. This lecture is intended to provide a basic overview of tumor invasion and metastasis. We will start with an introduction to the steps of the metastatic cascade, including a review of foundational experimental and clinical evidence that has led to our current understanding of this process. We will then cover the fundamentals of tumor progression, as it relates to metastatic heterogeneity, and review evidence supporting Stephen Paget’s original “seed and soil” hypothesis. With this knowledge we will move into examples of how stromal and immune cells may interact with tumor cells to regulate or facilitate individual steps of the metastatic cascade. Finally, we will review current concepts and trends in metastasis research including the potential fate of disseminated tumor cells, importance of the metastatic niche, reactivation of dormancy, and implications for the clinical therapy of metastasis.   

Learning Objectives

• Recall the steps of the metastatic cascade and the 'decathlon' analogy
• Assimilate the fundamental experiments that have led to our understanding of the metastatic cascade
• Provide an example of paracrine signaling or cross-talk between tumor tissues and stromal tissues/immune cells and explain how this might lead to tumor progression or metastasis
• Recognize strengths and shortcomings of common in vitro and in vivo techniques capable of evaluating metastasis
• Understand the clinical implications (and limitations) of detecting tumor cells within the circulation, regional nodes or distant tissues
• Assimilate and discuss with clients, in lay terms, the metastatic cascade and how it relates to their pet's recommended treatment
• Recognize and define the concepts of "seed and soil", "foraging", tumor heterogeneity, exosomes and tumor dormancy