Short CommunicationA simple method for measuring interstitial fluid pressure in cancer tissues
Introduction
When a piece of bark is peeled off a transpiring tree and a cut is made in the xylem, no sap runs out; in fact, a drop of water placed on the cut is drawn in for the sap is under negative pressure. Similarly, when the subcutaneous tissue of an animal is exposed, fluid does not seep out since the interstitial fluid is under negative pressure. In normal subcutaneous tissue, the interstitial fluid pressure (IFP) is negative (Scholander et al., 1968). By contrast, IFP is often increased in tumor tissue (Young et al., 1950) and forms a barrier against efficient drug delivery into the tumor (Jain, 1987a, Jain, 1987b). There are several techniques described for IFP measurements, all of which require experience to use ramified instrumentation and surgical procedures. They include: wick catheter (Scholander et al., 1968, Hargens, 1981, Mubarak and Hargens, 1981), modified wick technique (wick-in-needle technique) (Fadnes et al., 1977, Wiig et al., 1987), servo-micropipette (Wiederhielm et al., 1964) for acute studies of IFP, and subcutaneous capsule implantation for 4–6 weeks (Guyton, 1963) allowing chronic tests of IFP.
Here, we describe a simplified procedure using a transducer-tipped catheter and a precision glide needle that allows reliable measurement of IFP in tumor tissues. We believe this technique will allow the researchers in the vascular biology field and clinicians in the oncology field to apply IFP measurement easily as a useful tool in research.
Section snippets
Materials and methods
In order to compare and validate the pressures obtained with the miniature pressure transducer with a well-established, conventional method (0.6 mm wick-in-needle) (Fadnes et al., 1977, Wiig et al., 1987), we simultaneously compared a needle-guided Millar SPC 320, 2F Mikro-Tip sensor (http://www.millarinstruments.com) and wick-in-needle probes side-by-side in a pilot study in two mice (C57BL/6) bearing B16F1 skin tumor grafts. For wick-in-needle technique, a 0.6 mm needle was provided with a
Results
Polyurethane ultraminiature pressure transducers, recognized for impeccable accuracy in the pressure range between −50 mm Hg to +300 mm Hg, provide a simple, accurate, and thromboresistant method of measuring the pressure at the source (Zimmer and Millar, 1998). Entire procedure of calibration of the sensor, introduction of the sensor into the tumor, and IFP reading does not take more than 10 min and can be performed with ease by anyone who can perform a subcutaneous injection. Our preliminary
Discussion
The interstitial fluid pressure within a tumor is actively regulated through interactions between cells and extracellular matrix molecules. Many anticancer drugs and antibodies used for treating patients with cancer are transported from the circulatory system through the interstitial space by convection (i.e. by streaming of a flowing fluid) rather than by diffusion. Increased tumor IFP causes inefficient uptake of therapeutic agents by decreasing convection. Cancer cells are therefore exposed
Critique of four IFP measurement techniques
The micropuncture (0.1 μm glass micropipette) technique does not allow for measurements in deep tissues; usually recordings can only be made down to about 1 mm from the surface (Wiederhielm, 1981, Adair et al., 1983). Furthermore, the glass micropipette breaks very easily during tissue penetration and from the slightest motion of the mouse. The wick catheter technique (Scholander et al., 1968) is vulnerable to clotting if there is extravasated blood within the tissue (Wiederhielm, 1981, Adair
Acknowledgments
This brief report is dedicated to P.F. Scholander, M.D., Ph.D. (1905–1980) who made pioneering contributions to the wealth of knowledge in the field of interstitial tissue fluid pressure. This work has been supported by grants from NIH (National Institute of Child Health and Human Development) RO3 HD044783, the U.S. Department of Defense Prostate Cancer Research Program New Investigator Award PC020822, and University of California, Tobacco-Related Disease Research Program Idea Award (TRDRP
References (29)
- et al.
Binding of the NG2 proteoglycan to type VI collagen and other extracellular matrix molecules
J. Biol. Chem.
(1996) - et al.
Interstitial fluid pressure in rats measured with a modified wick technique
Microvasc. Res.
(1977) - et al.
The membrane-spanning proteoglycan NG2 binds to collagens V and VI through the central nonglobular domain of its core protein
J. Biol. Chem.
(1997) - et al.
Techniques in Measurement of Tissue Fluid Pressures and Lymph Flow
(1983) - et al.
Interstitial hypertension in superficial metastatic melanomas in humans
Cancer Res.
(1991) Altering the genome by homologous recombination
Science
(1989)- et al.
NG2 proteoglycan promotes endothelial cell motility and angiogenesis via engagement of galectin-3 and alpha3beta1 integrin
Mol. Biol. Cell
(2004) - et al.
PDGF (alpha)-receptor is unresponsive to PDGF-AA in aortic smooth muscle cells from the NG2 knockout mouse
J. Cell Sci.
(1999) A concept of negative interstitial pressure based on pressures in implanted perforated capsules
Circ. Res.
(1963)Introduction and historical perspectives
High interstitial fluid pressure—An obstacle in cancer therapy
Nat. Rev. Cancer
Transport of molecules in the tumor interstitium: a review
Cancer Res.
Transport of molecules across tumor vasculature
Cancer Metastasis Rev.
Reduction of interstitial fluid pressure after TNF-alpha treatment of three human melanoma xenografts
Br. J. Cancer
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2018, Computers in Biology and MedicineCitation Excerpt :Interstitial fluid velocity (IFV) created by IFP is also an important parameter for drug delivery and a parameter that affects the metastastatic nature of a tumor as it measures fluid transport inside the tumor [34]. To date, there are only a few invasive methods that can be used to estimate IFP in tissues [7,48]. Dynamic contrast enhanced MRI has been investigated as a possible tool for imaging IFP and IFV in tissues but with limited success [24–26,40].