The human tumor microenvironment: invasive (needle) measurement of oxygen and interstitial fluid pressure

https://doi.org/10.1016/j.semradonc.2004.04.006Get rights and content

Abstract

Invasive needle-based assessments of the extracellular environment in human tumors have yielded important prognostic information that has shaped the direction of future translational research and begun to influence clinical practice. This review focuses on electrode measurements of oxygenation in human tumors, particularly in relation to the practicalities of applying these techniques in the clinic and the relationship to patient outcome. Elevated tumor interstitial fluid pressure (IFP) has been shown to be an important independent prognostic factor in cervix cancer. The pathophysiology of elevated IFP is discussed, along with possible explanations for the strong influence on patient outcome and directions for future research.

Section snippets

Technical considerations

Polarographic electrode measurements of tumor oxygenation have now been described for a number of human malignancies, including breast, cervix, head and neck, pancreatic, prostate and vulvar carcinomas, as well as soft-tissue sarcoma of the extremities and central nervous system tumors.5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 These measurements have provided valuable information about the behavior of human malignancies, and electrode-based techniques remain the gold standard for assessing

Pathophysiology

The IFP in most normal tissues is close to atmospheric pressure but significantly elevated in most solid malignant tumors. Values in the range of 10 to 100 mm Hg have been documented in a variety of human malignancies.4, 41, 42, 43, 44, 45, 46 The pathophysiology of elevated IFP has been extensively studied using mathematical models of transcapillary and interstitial fluid flow47, 48, 49, 50 and experiments in animal tumors.50, 51, 52, 53, 54

IFP is elevated in tumors as a result of both the

References (72)

  • V. Rudat et al.

    Repeatability and prognostic impact of the pretreatment pO(2) histography in patients with advanced head and neck cancer

    Radiother Oncol

    (2000)
  • D.M. Brizel et al.

    Oxygenation of head and neck cancerChanges during radiotherapy and impact on treatment outcome

    Radiother Oncol

    (1999)
  • M. Nordsmark et al.

    Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck

    Radiother Oncol

    (1996)
  • P. Stadler et al.

    Influence of the hypoxic subvolume on the survival of patients with head and neck cancer

    Int J Radiat Oncol Biol Phys

    (1999)
  • M. Nordsmark et al.

    Invasive oxygen measurements and pimonidazole labeling in human cervix carcinoma

    Int J Radiat Oncol Biol Phys

    (2001)
  • L. Baxter et al.

    Transport of fluid and macromolecules in tumors. I. Role of interstitial pressure and convection

    Microvasc Res

    (1989)
  • M.F. Milosevic et al.

    The relationship between elevated interstitial fluid pressure and blood flow in tumorsA bioengineering analysis

    Int J Radiat Oncol Biol Phys

    (1999)
  • F. Mollica et al.

    A model for temporal heterogeneities of tumor blood flow

    Microvasc Res

    (2003)
  • Y. Boucher et al.

    Lack of general correlation between interstitial fluid pressure and oxygen partial pressure in solid tumors

    Microvasc Res

    (1995)
  • M.W. Dewhirst

    Concepts of oxygen transport at the microcirculatory level

    Semin Radiat Oncol

    (1998)
  • K. Pietras et al.

    PDGF receptors as cancer drug targets

    Cancer Cell

    (2003)
  • R.S. Bush et al.

    Definitive evidence for hypoxic cells influencing cure in cancer therapy

    Br J Cancer

    (1978)
  • J. Overgaard

    Clinical evaluation of nitroimidazoles as modifiers of hypoxia in solid tumors

    Oncol Res

    (1994)
  • P. Vaupel et al.

    Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumorsA review

    Cancer Res

    (1989)
  • M. Milosevic et al.

    Interstitial fluid pressure predicts survival in patients with cervix cancer independent of clinical prognostic factors and tumor oxygen measurements

    Cancer Res

    (2001)
  • B. Movsas et al.

    Increasing levels of hypoxia in prostate carcinoma correlate significantly with increasing clinical stage and patient ageAn Eppendorf pO(2) study

    Cancer

    (2000)
  • D.M. Brizel et al.

    Tumor oxygenation predicts for likelihood of distant metastases in human soft tissue sarcoma

    Cancer Res

    (1996)
  • A. Fyles et al.

    Tumor hypoxia has independent predictor impact only in patients with node-negative cervix cancer

    J Clin Oncol

    (2002)
  • M. Hockel et al.

    Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix

    Cancer Res

    (1996)
  • H. Lyng et al.

    Disease control of uterine cervical cancerRelationships to tumor oxygen tension, vascular density, cell density, and frequency of mitosis and apoptosis measured before treatment and during radiotherapy

    Clin Cancer Res

    (2000)
  • M. Nordsmark et al.

    Hypoxia in human soft tissue sarcomasAdverse impact on survival and no association with p53 mutations

    Br J Cancer

    (2001)
  • P. Vaupel et al.

    Oxygenation of human tumorsEvaluation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements

    Cancer Res

    (1991)
  • A.I. Minchinton et al.

    Beware the Eppendorf pO2 histograph!

    (1999)
  • M. Nordsmark et al.

    Measurement of human tumour oxygenation status by a polarographic needle electrode. An analysis of inter- and intratumour heterogeneity

    Acta Oncol

    (1994)
  • J.L. Fleiss

    Statistical Methods for Rates and Proportions

    (1981)
  • J.M. Brown

    Evidence for acutely hypoxic cells in mouse tumours, and a possible mechanism for reoxygenation

    Br J Radiol

    (1979)
  • Cited by (147)

    • Ultrasound robotics for precision therapy

      2024, Advanced Drug Delivery Reviews
    • Tumor microenvironment-responsive dynamic inorganic nanoassemblies for cancer imaging and treatment

      2021, Advanced Drug Delivery Reviews
      Citation Excerpt :

      Notably, the neovasculature produced in tumor presents some abnormalities (e.g. absent or incomplete basement membranes and endothelial cell layers) [17–19], making them hyper-permeable [20]. Such abnormal new vessels, meanwhile, show low resistance to lymphatics flow but high resistance to capillary blood flow [21,22], resulting in a net outflow of fluid into the surrounding inter-tissue space in the solid tumor. The lack of functional lymphatics in the tumor further increases fluid accumulation, distends the elastic extracellular matrix, increases interstitial pressure, and reduces fluid movement through the interstitium [22].

    View all citing articles on Scopus

    Supported in part by the National Cancer Institute of Canada with funds from the Terry Fox Run.

    View full text