ScienceVEGF

Why is interstitial pressure important?

Interstitial pressure in tumours

With the exception of the periphery of a tumour, where interstitial pressure remains at close to normal levels, the interstitial pressure within a tumour is remarkably high. Large molecules, such as therapeutic agents, tend to travel by convection (from areas of high pressure to areas of low pressure). At areas of low interstitial pressure, such as the periphery of a tumour, agents are easily able to leave the bloodstream and enter surrounding cells because the pressure in the blood vessels is greater than the pressure in the interstitium. When interstitial pressure is higher, it may exceed pressure in the vasculature. As a consequence, convection virtually ceases, and delivery of agents from the bloodstream to tumour cells is impeded.^68–70

Jain RK. Sci Am 1994;271:58–65.

Tumours are not composed entirely of malignant cells. In fact, less than half of a tumour's volume may be cancer cells, 1–10% may be blood vessels, and the remainder is interstitium, a collagen-rich matrix that surrounds cancer cells and separates them from the vasculature.^68,71

Tumour vasculature is leaky due to gaps between endothelial cells and openings within the cells themselves.⁷² Because of the hyperpermeable nature of VEGF-induced vasculature, fluid can leak from tumour vessels into the interstitium.^7,68 The result is remarkably high interstitial pressure throughout the interior of a tumour, while pressure in the outermost areas remains at close to normal levels.⁶⁸ By contrast, pressure in veins (the predominant vessels in tumours) is reduced in tumour veins compared with veins in normal tissue. Thus, there is a dual effect of increased interstitial pressure and decreased vascular pressure in tumours.⁷⁰

Since high molecular-weight molecules, including therapeutic agents, travel in large part by convection (from areas of high pressure to areas of low pressure), the high interstitial pressure of tumours can impede the delivery of therapeutic agents from the bloodstream to tumour cells.⁶⁸

High interstitial pressure has been demonstrated in a variety of tumour types, as shown below.⁶⁸