Importance of interstitial pressure

Interstitial pressure in tumors¹

With the exception of the periphery of a tumor, where interstitial pressure remains at close to normal levels, the interstitial pressure within a tumor is remarkably high.²

Jain RK. Sci Am. 1994;271:58-65.

Tumors are not composed entirely of malignant cells. In fact, less than half of a tumor's volume may be cancer cells, 1% to 10% may be blood vessels, and the remainder is interstitium, a collagen-rich matrix that surrounds cancer cells and separates them from the vasculature.^2,3

The vasculature induced by vascular endothelial growth factor (VEGF) is leaky due to gaps between endothelial cells and openings within the cells themselves.^4,5 Because of the hyperpermeable nature of VEGF-induced vasculature, fluid can leak from tumor vessels into the interstitium.^2,6 The result is remarkably high interstitial pressure throughout the interior of a tumor, while pressure in the outermost areas remains at close to normal levels.² By contrast, pressure in veins—the predominant vessels in tumors—is reduced in tumor veins compared with veins in normal tissue. Thus, there is a dual effect of increased interstitial pressure and decreased vascular pressure in tumors.³

High interstitial pressure has been demonstrated in a variety of tumor types, as shown below.²

References:

1.

Thakker GD, Hajjar DP, Muller WA, et al. J Biol Chem. 1999;274:10002-10007.

2.

Jain RK. Sci Am. 1994;271:58-65.

3.

Jain RK. Cancer Res. 1987;47:3039-3051.

4.

Inai T, Mancuso M, Hashizume H, et al. Am J Pathol. 2004;165:35-52.

5.

Baluk P, Hashizume H, McDonald DM. Curr Opin Genet Devel. 2005;15:102-111.

6.

Jain RK. Nat Med. 2001;7:987-989.