Interstitial fluid pressure in tumors: therapeutic barrier and biomarker of angiogenesis

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

Bibiiography

• 1  Bristow RG, Hill RP: Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat. Rev. Cancer8,180–192 (2008).
  Medline CASGoogle Scholar
• 2  Cairns R, Papandreou I, Denko N: Overcoming physiologic barriers to cancer treatment by molecularly targeting the tumor microenvironment. Mol. Cancer Res.4,61–70 (2006).
  Medline CASGoogle Scholar
• 3  Moeller BJ, Richardson RA, Dewhirst MW: Hypoxia and radiotherapy: opportunities for improved outcomes in cancer treatment. Cancer Metastasis Rev.26,241–248 (2007).
  Medline CASGoogle Scholar
• 4  Jain RK, Duda DG, Clark JW, Loeffler JS: Lessons from Phase III clinical trials on anti-VEGF therapy for cancer. Nat. Clin. Pract. Oncol.3,24–40 (2006).
  Medline CASGoogle Scholar
• 5  Milosevic M, Fyles A, Hedley D et al.: Interstitial fluid pressure predicts survival in patients with cervix cancer independent of clinical prognostic factors and tumor oxygen measurements. Cancer Res.61,6400–6405 (2001).▪▪ The only large-scale clincial study of interstitial fluid pressure (IFP) as a predictor of patient outcome following radiotherapy.
  Medline CASGoogle Scholar
• 6  Fyles A, Milosevic M, Pintilie M et al.: Long-term performance of interstitial fluid pressure and hypoxia as prognostic factors in cervix cancer. Radiother. Oncol.80,132–137 (2006).▪ Mature results of a large clincial study showing the sustained, independent predictive value of pretreatment IFP measurements in cervical cancer.
  MedlineGoogle Scholar
• 7  Heldin CH, Rubin K, Pietras K, Ostman A: High interstitial fluid pressure – an obstacle in cancer therapy. Nat. Rev. Cancer4,806–813 (2004).▪ Excellent summary of the tumor interstitium as a determinant of IFP and drug uptake.
  Medline CASGoogle Scholar
• 8  Taghian AG, Abi-Raad R, Assaad SI et al.: Paclitaxel decreases the interstitial fluid pressure and improves oxygenation in breast cancers in patients treated with neoadjuvant chemotherapy: clinical implications. J. Clin. Oncol.23,1951–1961 (2005).
  Medline CASGoogle Scholar
• 9  Boucher Y, Kirkwood JM, Opacic D: Interstitial hypertension in superficial metastatic melanomas in humans. Cancer Res.51,6691–6694 (1991).
  Medline CASGoogle Scholar
• 10  Curti BD, Urba WJ, Alvord WG et al.: Interstitial pressure of subcutaneous nodules in melanoma and lymphoma patients: changes during treatment. Cancer Res.53,2204–2207 (1993).
  Medline CASGoogle Scholar
• 11  Gutmann R, Leunig M, Feyh J et al.: Interstitial hypertension in head and neck tumors in patients: correlation with tumor size. Cancer Res.52,1993–1995 (1992).
  Medline CASGoogle Scholar
• 12  Nathan SS, DiResta GR, Casas-GanemJE et al.: Elevated physiologic tumor pressure promotes proliferation and chemosensitivity in human osteosarcoma. Clin. Cancer Res.11,2389–2397 (2005).▪ Clincial and preclinical study of high IFP as a cause of tumor proliferation and increased sensitivity to cisplatin chemotherapy.
  Medline CASGoogle Scholar
• 13  Jain RK: Determinants of tumor blood flow: a review. Cancer Res.48,2641–2658 (1988).
  Medline CASGoogle Scholar
• 14  Padera TP, Stoll BR, Tooredman JB, Capen D, di Tomaso E, Jain RK: Pathology: cancer cells compress intratumour vessels. Nature427,695 (2004).
  Medline CASGoogle Scholar
• 15  Denko NC, Giaccia AJ: Tumor hypoxia, the physiological link between Trousseau’s syndrome (carcinoma-induced coagulopathy) and metastasis. Cancer Res.61,795–798 (2001).
  Medline CASGoogle Scholar
• 16  Jain RK: Transport of molecules in the tumor interstitium: a review. Cancer Res.47,3039–3051 (1987).
  Medline CASGoogle Scholar
• 17  Wiig H, Rubin K, Reed RK: New and active role of the interstitium in control of interstitial fluid pressure: potential therapeutic consequences. Acta Anaesthesiol. Scand.47,111–121 (2003).
  Medline CASGoogle Scholar
• 18  Leu AJ, Berk DA, Lymboussaki A, Alitalo K, Jain RK: Absence of functional lymphatics within a murine sarcoma: a molecular and functional evaluation. Cancer Res.60,4324–4327 (2000).
  Medline CASGoogle Scholar
• 19  Baxter L, Jain R: Transport of fluid and macromolecules in tumors I. Role of interstitial pressure and convection. Microvasc. Res.37,77–104 (1989).▪▪ First biophysical description of the cause of elevated IFP in tumors.
  Medline CASGoogle Scholar
• 20  Boucher Y, Baxter LT, Jain RK: Interstitial pressure gradients in tissue isolated and subcutaneous tissues: implications for therapy. Cancer Res.50,4478–4484 (1990).
  Medline CASGoogle Scholar
• 21  Boucher Y, Jain RK: Microvascular pressure is the principal driving force for interstitial hypertension in solid tumors: implications for vascular collapse. Cancer Res.52,5110–5114 (1992).
  Medline CASGoogle Scholar
• 22  Guyton AC: Textbook of Medical Physiology. Sixth edition. WB Saunders Company, PA, USA (1981).
  Google Scholar
• 23  Lunt SJ, Kalliomaki TM, Brown A, Yang VX, Milosevic M, Hill RP: Interstitial fluid pressure, vascularity and metastasis in ectopic, orthotopic and spontaneous tumours. BMC Cancer8,2 (2008).
  MedlineGoogle Scholar
• 24  Milosevic MF, Fyles AW, Wong R et al.: Interstitial fluid pressure in cervical carcinoma: within tumor heterogeneity, and relation to oxygen tension. Cancer82,2418–2426 (1998).
  Medline CASGoogle Scholar
• 25  DiResta GR, Lee J, Larson SM, Arbit E: Characterization of neuroblastoma xenograft in rat flank. I. Growth, interstitial fluid pressure, and interstitial fluid velocity distribution profiles. Microvasc. Res.46,158–177 (1993).
  Medline CASGoogle Scholar
• 26  Rofstad EK, Tunheim SH, Mathiesen B et al.: Pulmonary and lymph node metastasis is associated with primary tumor interstitial fluid pressure in human melanoma xenografts. Cancer Res.62,661–664 (2002).
  Medline CASGoogle Scholar
• 27  Griffon-Etienne G, Boucher Y, Jain RK, Suit HD: Effects of needle insertion in tumors on interstitial fluid pressure. Microvasc. Res.54,174–177 (1997).
  Medline CASGoogle Scholar
• 28  Skliarenko J, Lunt SJ, Gordon ML, Vitkin A, Milosevic M, Hill RP: Effects of the vascular targeting agent ZD6126 on interstitial fluid pressure and cell survival in tumors. Cancer Res.66,2074–2080 (2006).
  Medline CASGoogle Scholar
• 29  Milosevic MF, Fyles AW, Hill RP: The relationship between elevated interstitial fluid pressure and blood flow in tumors: a bioengineering analysis. Int. J. Radiat. Oncol. Biol. Phys.43,1111–1123 (1999).
  Medline CASGoogle Scholar
• 30  Ozerdem U, Hargens AR: A simple method for measuring interstitial fluid pressure in cancer tissues. Microvasc. Res.70,116–120 (2005).
  Medline CASGoogle Scholar
• 31  Schnell CR, Stauffer F, Allegrini PR et al.: Effects of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 on the tumor vasculature: implications for clinical imaging. Cancer Res.68,6598–6607 (2008).
  Medline CASGoogle Scholar
• 32  Haider M, Sitartchouk I, Roberts TPL, Fyles A, Hashmi AT, Milosevic M: Correlations between dynamic contrast enhanced magnetic resonance imaging derived measures of tumor microvasculature and interstitial fluid pressure in patients with cervix cancer. J. Magn. Reson. Imaging25,153–159 (2007).
  MedlineGoogle Scholar
• 33  McVeigh PZ, Syed AM, Milosevic M, Fyles A, Haider MA: Diffusion-weighted MRI in cervical cancer. Eur. Radiol.18,1058–1064 (2008).
  MedlineGoogle Scholar
• 34  Hassid Y, Furman-Haran E, Margalit R, Eilam R, Degani H: Noninvasive magnetic resonance imaging of transport and interstitial fluid pressure in ectopic human lung tumors. Cancer Res.66,4159–4166 (2006).▪ An approach to measuring IFP noninvasively using magnetic resonance imaging.
  Medline CASGoogle Scholar
• 35  Milosevic M, Lunt SJ, Leung E et al.: Interstitial permeability and elasticity in human cervix cancer. Microvasc. Res.75,381–390 (2008).
  Medline CASGoogle Scholar
• 36  Hori K, Saito S: Microvascular mechanisms by which the combretastatin A-4 derivative AC7700 (AVE8062) induces tumour blood flow stasis. Br. J. Cancer89,1334–1344 (2003).
  Medline CASGoogle Scholar
• 37  Tong RT, Boucher Y, Kozin SV, Winkler F, Hicklin DJ, Jain RK: Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors. Cancer Res.64,3731–3736 (2004).
  Medline CASGoogle Scholar
• 38  Lee C, Heijn M, di Tomaso E et al.: Anti-vascular endothelial growth factor treatment augments tumor radiation response under normoxic and hypoxic conditions. Cancer Res.60,5565–5570 (2000).
  Medline CASGoogle Scholar
• 39  Wilhelm SM, Carter C, Tang L et al.: BAY 43–9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res.64,7099–7109 (2004).
  Medline CASGoogle Scholar
• 40  Pietras K, Ostman A, Sjoquist M et al.: Inhibition of platelet-derived growth factor receptors reduces interstitial hypertension and increases transcapillary transport in tumors. Cancer Res.61,2929–2934 (2001).
  Medline CASGoogle Scholar
• 41  Willett CG, Boucher Y, di Tomaso E et al.: Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat. Med.10,145–147 (2004).▪ Clincial evidence that IFP can be used as a biomarker of response to anti-angiogenic treatment.
  Medline CASGoogle Scholar
• 42  Winkler F, Kozin SV, Tong RT et al.: Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell6,553–563 (2004).
  Medline CASGoogle Scholar
• 43  Pietras K, Stumm M, Hubert M et al.: STI571 enhances the therapeutic index of epothilone B by a tumor-selective increase of drug uptake. Clin. Cancer Res.9,3779–3787 (2003).▪▪ Preclincial study of lowering IFP as a means of enhancing chemotherapy uptake and efficacy.
  Medline CASGoogle Scholar
• 44  Jain RK: Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science307,58–62 (2005).
  Medline CASGoogle Scholar
• 45  Vlahovic G, Rabbani ZN, Herndon JE 2nd, Dewhirst MW, Vujaskovic Z: Treatment with Imatinib in NSCLC is associated with decrease of phosphorylated PDGFR-beta and VEGF expression, decrease in interstitial fluid pressure and improvement of oxygenation. Br. J. Cancer95,1013–1019 (2006).
  Medline CASGoogle Scholar
• 46  Wildiers H, Guetens G, De Boeck G et al.: Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11. Br. J. Cancer88,1979–1986 (2003).
  Medline CASGoogle Scholar
• 47  Dickson PV, Hamner JB, Sims TL et al.: Bevacizumab-induced transient remodeling of the vasculature in neuroblastoma xenografts results in improved delivery and efficacy of systemically administered chemotherapy. Clin. Cancer Res.13,3942–3950 (2007).
  Medline CASGoogle Scholar
• 48  Fyles A, Milosevic M, Hedley D et al.: Tumor hypoxia has independent predictor impact only in patients with node-negative cervix cancer. J. Clin. Oncol.20,680–687 (2002).
  Medline CASGoogle Scholar
• 49  Fyles A, Keane TJ, Barton M, Simm J: The effect of treatment duration in the local control of cervix cancer. Radiother. Oncol.25,273–279 (1992).
  Medline CASGoogle Scholar
• 50  Diresta GR, Nathan SS, Manoso MW et al.: Cell proliferation of cultured human cancer cells are affected by the elevated tumor pressures that exist in vivo. Ann. Biomed. Eng.33,1270–1280 (2005).
  MedlineGoogle Scholar
• 51  Boucher Y, Lee I, Jain RK: Lack of general correlation between interstitial fluid pressure and oxygen partial pressure in solid tumors. Microvasc. Res.50,175–182 (1995).
  Medline CASGoogle Scholar
• 52  Mollica F, Jain RK, Netti PA: A model for temporal heterogeneities of tumor blood flow. Microvasc. Res.65,56–60 (2003).
  MedlineGoogle Scholar
• 53  Baish JW, Netti PA, Jain RK: Transmural coupling of fluid flow in microcirculatory network and interstitium in tumors. Microvasc. Res.53,128–141 (1997).
  Medline CASGoogle Scholar
• 54  Gorski DH, Beckett MA, Jaskowiak NT et al.: Blockade of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res.59,3374–3378 (1999).
  Medline CASGoogle Scholar
• 55  Nathan SS, Huvos AG, Casas-Ganem JE et al.: Tumor interstitial fluid pressure may regulate angiogenic factors in osteosarcoma. J. Orthop. Res.26(11),1520–1525 (2008).▪ Preclinical study indicating that hydrostatic pressure may directly inhibit angiogenesis and stimulate lymphangiogenesis in tumors.
  MedlineGoogle Scholar
• 56  Manome Y, Saeki N, Yoshinaga H, Watanabe M, Mizuno S: A culture device demonstrates that hydrostatic pressure increases mRNA of RGS5 in neuroblastoma and CHC1-L in lymphocytic cells. Cells Tissues Organs174,155–161 (2003).
  Medline CASGoogle Scholar
• 57  Hamzah J, Jugold M, Kiessling F et al.: Vascular normalization in Rgs5-deficient tumours promotes immune destruction. Nature453,410–414 (2008).
  Medline CASGoogle Scholar
• 58  Jain RK, Tong RT, Munn LL: Effect of vascular normalization by antiangiogenic therapy on interstitial hypertension, peritumor edema, and lymphatic metastasis: insights from a mathematical model. Cancer Res.67,2729–2735 (2007).
  Medline CASGoogle Scholar
• 59  Timke C, Zieher H, Roth A et al.: Combination of vascular endothelial growth factor receptor/platelet-derived growth factor receptor inhibition markedly improves radiation tumor therapy. Clin. Cancer Res.14,2210–2219 (2008).
  Medline CASGoogle Scholar
• 60  Pietras K, Rubin K, Sjoblom T et al.: Inhibition of PDGF receptor signaling in tumor stroma enhances antitumor effect of chemotherapy. Cancer Res.62,5476–5484 (2002).
  Medline CASGoogle Scholar
• 61  Vlahovic G, Ponce AM, Rabbani Z et al.: Treatment with imatinib improves drug delivery and efficacy in NSCLC xenografts. Br. J. Cancer97,735–740 (2007).
  Medline CASGoogle Scholar
• 62  Chiu JJ, Usami S, Chien S: Vascular endothelial responses to altered shear stress: pathologic implications for atherosclerosis. Ann. Med.1–10 (2008).
  Google Scholar