Interstitial Hypertension Suppresses Escape of Human Breast Tumor Cells Via Convection of Interstitial Fluid

Introduction-Interstitial hypertension, a rise in interstitial fluid pressure, is a common feature of many solid tumors as they progress to an invasive state. It is currently unclear whether this elevated pressure alters the probability that tumor cells eventually escape into a neighboring blood or lymphatic vessel. Methods-In this study, we analyze the escape of MDA-MB-231 human breast tumor cells from a similar to 3-mm-long preformed aggregate into a 120-mu m-diameter empty cavity in a micromolded type I collagen gel. The "micro-tumors" were located within similar to 300 mu m of one or two cavities. Pressures of similar to 0.65 cm H2O were applied only to the tumor ("interstitial hypertension") or to its adjacent cavity. Results-This work shows that interstitial hypertension suppresses escape into the adjacent cavity, but not because tumor cells respond directly to the pressure profile. Instead, hypertension alters the chemical microenvironment at the tumor margin to one that hampers escape. Administration of tumor interstitial fluid phenocopies the effects of hypertension. Conclusions- This work uncovers a link between tumor pressure, interstitial flow, and tumor cell escape in MDA-MB-231 cells, and suggests that interstitial hypertension serves to hinder further progression to metastatic escape.