Circulating Tumor Cells: When a Solid Tumor Meets a Fluid Microenvironment.

Solid tumor dissemination from the primary site to the sites of metastasis involves tumor cell transport through the blood or lymph circulation systems. Once the tumor cells enter the bloodstream, they encounter a new hostile microenvironment. The cells must withstand hemodynamic forces and overcome the effects of fluid shear. The cells are exposed to immunological signaling insults from leukocytes, to collisions with erythrocytes, and to interactions with platelets or macrophages. Finally, the cells need to attach to the blood vessel walls and extravasate to the surrounding stroma to form tumor metastases. Although only a small fraction of invasive cells is able to complete the metastatic process, most cancer-related deaths are the result of tumor metastasis. Thus, investigating the intracellular properties of circulating tumor cells and the extracellular conditions that allow the tumor cells to survive and thrive in this microenvironment is of vital interest. In this chapter, we discuss the intravascular microenvironment that the circulating tumor cells must endure. We summarize the current experimental and computational literature on tumor cells in the circulation system. We also illustrate various aspects of the intravascular transport of circulating tumor cells using a mathematical model based on immersed boundary principles.