Fibrogenesis & Tissue Repair


Open Access Short review

Interstitial fluid: the overlooked component of the tumor microenvironment?

Helge Wiig1,2*, Olav Tenstad1, Per O Iversen3, Raghu Kalluri2 and Rolf Bjerkvig1

Author Affiliations

1 Department of Biomedicine, University of Bergen, Bergen, Norway

2 Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, MA, USA

3 Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway

For all author emails, please log on.

Fibrogenesis & Tissue Repair 2010, 3:12 doi:10.1186/1755-1536-3-12

Published: 23 July 2010

Abstract

Background

The interstitium, situated between the blood and lymph vessels and the cells, consists of a solid or matrix phase and a fluid phase, together constituting the tissue microenvironment. Here we focus on the interstitial fluid phase of tumors, i.e., the fluid bathing the tumor and stromal cells. Novel knowledge on this compartment may provide important insight into how tumors develop and how they respond to therapy.

Results

We discuss available techniques for interstitial fluid isolation and implications of recent findings with respect to transcapillary fluid balance and uptake of macromolecular therapeutic agents. By the development of new methods it is emerging that local gradients exist in signaling substances from neoplastic tissue to plasma. Such gradients may provide new insight into the biology of tumors and mechanistic aspects linked to therapy. The emergence of sensitive proteomic technologies has made the interstitial fluid compartment in general and that of tumors in particular a highly valuable source for tissue-specific proteins that may serve as biomarker candidates. Potential biomarkers will appear locally at high concentrations in the tissue of interest and will eventually appear in the plasma, where they are diluted.

Conclusions

Access to fluid that reliably reflects the local microenvironment enables us to identify substances that can be used in early detection and monitoring of disease.