Opportunities for Studying the Hydrodynamic Context for Breast Cancer Cell Spread Through Lymph Flow

Background: The lymphatic system is an extensive vascular network that serves as the primary route for the metastatic spread of breast cancer cells (BCCs). However, the dynamics by which BCCs (10-40 μm) travel in the lymphatics (100-300 μm) to distant sites, and eventually establish metastatic tumors, remain poorly understood. The lymphatic flow environment is extremely complex, and despite the number of studies carried out in recent years, an accurate description remains unclear. Methods and Results: Over the past two decades, significant advancements have been made in characterizing lymphatic flow, using numerical and experimental approaches, however, none of these studies addresses the dynamics of BCCs flowing in lymph. This review summarizes the flow environment metastatic BCCs are exposed to in the lymphatics. Special attention is paid to the flow behavior of cells/particles in microdevices in an attempt to elucidate the behavior of BCCs under lymph flow conditions (Reynolds number <1). The advection of BCCs in microflows is governed by the hydrodynamic forces present in the flow. Conclusions: A scarcity of information exists with regard to BCC advection in the lymphatics and this review highlights important areas for future research. A fundamental understanding of the response of BCCs to the forces in the lymphatics needs to be established. More comprehensive theoretical and experimental techniques are needed to quantify the effect of the lymphatic hydrodynamic forces on the behavior of BCCs, resulting in a more concrete basis for the numerical simulation of flow-induced shear stresses experienced by BCC membranes.