<p>In this short review paper, I describe the parallels of my own research career in cardiovascular engineering with Rakesh Jain’s career devoted to cancer research. It begins with our initial training in chemical engineering at the University of Delaware followed by Rakesh’s early focus on drug delivery to tumors and my early work on the fluid mechanics of artificial hearts. My subsequent studies of blood flow and macromolecular transport in arteries and atherosclerosis led to a new focus on interstitial flow within the arterial wall that intersected with Rakesh’s early studies of interstitial flow in the tumor microenvironment. Beginning in 1998 I spent a sabbatical year with Rakesh at the Steele Lab using <i>in vitro</i> endothelial cell monolayers to study the effects of vascular endothelial growth factor (VEGF) on albumin permeability and hydraulic conductivity. The Jain lab’s seminal work on anti-VEGF therapy for solid tumors continues to this day with a focus on delivery of chimeric antigen receptor (CAR)-T cells for solid tumors.</p><p>In parallel work my lab investigated the role of the endothelial cell surface glycoprotein layer (glycocalyx) in the mechanotransduction of blood flow shear stress and demonstrated the central role of heparan sulfate proteoglycans in flow induced nitric oxide production and changes in permeability and cell adhesion. This background led to studies of the cancer cell glycocalyx in collaboration with the Steele Lab. We observed the glycocalyx on cancer cells <i>in vitro</i> and showed that interstitial flow forces enhanced cancer cell motility by inducing matrix degrading enzyme production. This led to a demonstration of the effectiveness of small molecule inhibitors of glycocalyx synthesis that blocked metastasis in animal models. The review concludes by encouraging future research attention to the glycocalyx in cancer development and metastasis.</p>