Skip to main content
SpringerLink
Log in

Tumor Microenvironment and Hyperthermia

  • Chapter
  • First Online:
Book cover Hyperthermic Oncology from Bench to Bedside

Abstract

Solid tumors have a more acidic and hypoxic microenvironment than normal tissue. This unfavorable microenvironment results from an imbalance in the oxygen supply and demand of the tumor tissue. To overcome hypoxia, the tumor induces a new vascular supply. This new vasculature, however, is inefficient and chaotic, resulting in preserving the factors that stimulated the neovascularization. This review focuses on these processes and particularly on angiogenesis, tumor vascular morphology, hypoxia, pH, and the metabolic-vascular events induced or following tumor tissue heating. The various mechanisms that either modulate tumor microenvironments or blood perfusion during hyperthermia are described, providing also the many clinical modalities that may enhance or sensitize cancer cells to heat.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Vaupel P. Tumor microenvironmental physiology and its implications for radiation oncology. Semin Radiat Oncol. 2004;14(3):198–206.

    Article  PubMed  Google Scholar 

  2. Vaupel PW, Kelleher DK. Pathophysiological and vascular characteristics of tumours and their importance for hyperthermia: heterogeneity is the key issue. Int J Hyperthermia. 2010;26(3):211–23.

    Article  CAS  PubMed  Google Scholar 

  3. Hall EJ, Giaccia AJ. Cell, tissue, and tumor kinetics. In: Hall EJ, Giaccia AJ, editors. Radiobiology for the radiologist. 7th ed. Philadeiphia: Lippencott, Williams & Wilkins; 2012. p. 372–90.

    Google Scholar 

  4. Wouters BG, Koritzinsky. The tumour microenvironment and cellular hypoxia responses. In: Joiner M, van der Kogel AJ, editors. Basic clinical radiobiology. 4th ed. London: Hodder Arnold; 2009. p. 217–32.

    Chapter  Google Scholar 

  5. Baronzio G, Barongio A, Crespi E, Freitas I. Effects of tumor microenvironment on hyperthermia, photodynamic and nanotherapy. In: Baronzio G, Fiorentini G, Cogle CR, editors. Cancer microenvironment and therapeutic implications. New York: Springer Science + Business Media B.V; 2009. p. 181–96. doi:10.1007/978-1-4020-9576-4.

    Google Scholar 

  6. Hall EJ, Giaccia AJ. The biology and exploitation of tumor hypoxia. In: Hall EJ, Giaccia AJ, editors. Radiobiology for the radiologist. 7th ed. Philadeiphia: Lippencott, Williams & Wilkins; 2012. p. 432–47.

    Google Scholar 

  7. Horsman MR, van der Kogel AJ. Therapeutic approachs to tumour hypoxia. In: Joiner M, van der Kogel AJ, editors. Basic clinical radiobiology. 4th ed. London: Hodder Arnold; 2009. p. 233–45.

    Chapter  Google Scholar 

  8. Vaupel P, Mayer A. Hypoxia in tumors: pathogenesis-related classification, characterization of hypoxia subtypes, and associated biological and clinical implications. Adv Exp Med Biol. 2014;812:19–24. doi:10.1007/978-1-4939-0620-8_3.

    Article  CAS  PubMed  Google Scholar 

  9. Vaupel P. Metabolic microenvironment of tumor cells: a key factor in malignant progression. Exp Oncol. 2010;32(3):125–7.

    CAS  PubMed  Google Scholar 

  10. Mayer A, Vaupel P. Hypoxia, lactate accumulation, and acidosis: siblings or accomplices driving tumor progression and resistance to therapy? Adv Exp Med Biol. 2013;789:203–9. doi:10.1007/978-1-4614-7411-1_28.

    Article  CAS  PubMed  Google Scholar 

  11. Kato Y, Ozawa S, Miyamoto C, Maehata Y, Suzuki A, Maeda T, Baba Y. Acidic extracellular microenvironment and cancer. Cancer Cell Int. 2013;13:89. doi:10.1186/1475-2867-13-89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Vaupel PW, Kelleher DK. Blood flow and associated pathophysiology of uterine cervix cancers: characterisation and relevance for localized hyperthermia. Int J Hyperthermia. 2012;28(6):518–27. doi:10.3109/02656736.2012.699134. Epub 2012 Jul 27.

    Article  PubMed  Google Scholar 

  13. Song CW. Effect of local hyperthermia on blood flow and microenvironment: a review. Cancer Res. 1984;44(Suppl):4721–30.

    Google Scholar 

  14. Song CW, Chelstrom LM, Sung JH. Effects of a second heating on tumor blood flow. Radiat Res. 1990;122:66–71.

    Article  CAS  PubMed  Google Scholar 

  15. Ward KA, Jain RK. Response of tumours to hyperglycaemia: characterization, significance and role in hyperthermia. Int J Hyperthermia. 1988;4:223–50.

    Article  CAS  PubMed  Google Scholar 

  16. Vaupel P. Tumor blood flow. In: Molls M, Vaupel P, editors. Blood perfusion and microenvironment of human tumors. Berlin/Heidelberg/New York: Springer; 2000. p. 41–6.

    Chapter  Google Scholar 

  17. Vaupel P, Kallinowski F. Physiological effects of hyperthermia. Recent Results Cancer. 1987;104:71–109.

    Article  CAS  Google Scholar 

  18. Reinhold HS, Endrich B. Tumor microcirculation as a target for hyperthermia. Int J Hyperthermia. 1986;2:11–137.

    Article  Google Scholar 

  19. Dudar TE, Jain RK. Differential response of normal and tumor microenvironment to hyperthermia. Cancer Res. 1984;44:605–12.

    CAS  PubMed  Google Scholar 

  20. Sun X, Xing L, Ling CC, Li GC. The effect of mild temperature hyperthermia on tumour hypoxia and blood perfusion: relevance for radiotherapy, vascular targeting and imaging. Int J Hyperthermia. 2010;26(3):224–31.

    Article  CAS  PubMed  Google Scholar 

  21. Jain RK, Ward-Hartley K. Tumor blood flow-characterization, modifications and role in hyperthermia. IEEE Trans Sonics Ultrason. 1984;31:504–26.

    Article  Google Scholar 

  22. Nishimura Y, Hiraoka M, Jo S, Akuta K, Yukawa Y, Shibamoto Y, et al. Microangiographic and histologic analysis of the effects of hyperthermia on murine tumor vasculature. Int J Radiat Oncol Biol Phys. 1988;15:411–20.

    Article  CAS  PubMed  Google Scholar 

  23. Evans SS, Frey M, Scheider DM, Bruce RA, Wang WC, Repasky EA, et al. Regulation of leukocyte-endothelial cell interaction in tumor immunity. In: Mihich E, Croce C, editors. The biology of tumors. New York: Plenum Press; 1998. p. 273–86.

    Chapter  Google Scholar 

  24. Fajardo LF, Prionas SD. Endothelial cells and hyperthermia. Int J Hyperthermia. 1994;3:347–53.

    Article  Google Scholar 

  25. Suit H, Shalek RJ. Response of spontaneous mammary carcinoma of the C3H mouse to X-irradiation given under conditions of local tissue anoxia. J Nat Cancer Inst. 1963;31:497–509.

    CAS  PubMed  Google Scholar 

  26. Field SB. In vivo aspects of hyperthermic oncology. In: Field SB, Hand JW, editors. An Introduction to the practical aspects of clinical hyperthermia. London/New York/Philadelphia: Taylor & Francis; 1990. p. 55–68.

    Google Scholar 

  27. Hill SA, Denekamp J. The effect of vascular occlusion on the thermal sensitisation of a mouse tumour. Br J Radiol. 1978;51:997–1002.

    Article  CAS  PubMed  Google Scholar 

  28. Stuart K. Chemoembolization in the management of liver tumors. Oncologist. 2003;8:425–37.

    Article  PubMed  Google Scholar 

  29. Tanaka Y, Yamamoto K, Nagata K. Effects of multimodal treatment and hyperthermia on hepatic tumors. Cancer Chemother Pharmacol (Suppl). 1998;1:111–14.

    Google Scholar 

  30. Horsman MR, Siemann DW. Significance of the tumour microenvironment in radiotherapy. In: Baronzio G, Fiorentini G, Cogle CR, editors. Cancer microenvironment and therapeutic implications. New York: Springer Science + Business Media B.V; 2009. p. 137–56. doi:10.1007/978-1-4020-9576-4.

    Google Scholar 

  31. Dickson JA, Calderwood SK. Thermosensitivity of neoplastic tissues in vivo. In: Storm FK, editor. Hyperthermia in cancer therapy. Boston: GK Hall Medical; 1983. p. 63–140.

    Google Scholar 

  32. Hasegawa T, Gu YH, Takahashi T, Hasegawa T, Tanaka Y. Effects of hyperthermia-induced changes in pH value on tumor response and thermotolerance. In: Kosaka M, Sugahara T, Schmidt KL, Simon E, editors. Thermotherapy for neoplasia, inflammation, and pain. Tokyo: Springer Verlag; 2001. p. 433–8.

    Chapter  Google Scholar 

  33. Shem BC, Dahl O. Thermal enhancement of ACNU and potentiation of thermochemotherapy with ACNU by hypertonic glucose in the BT A rat glioma. J Neuroncol. 1991;10:247–52.

    Google Scholar 

  34. Lippmann HG, Graichen D. Glucose and K balance during high dosage intravenous glucose infusion. Infusionsther Klin Ernahr. 1977;4:166–78.

    Google Scholar 

  35. Nagata K, Murata T, Shiga T, Isoda H, Aoki Y, Yamamoto K, et al. Enhancement of thermoradiotherapy by glucose administration for superficial malignant tumours. Int J Hyperthermia. 1998;14:157–67.

    Article  CAS  PubMed  Google Scholar 

  36. Engin K, Leeper DB, Cater JR, Thistlethwaite AJ, Tupchong L, McFarlane JD. Extracellular pH distribution in human tumors. Int J Hyperthermia. 1995;11:211–16.

    Article  CAS  PubMed  Google Scholar 

  37. Han JS, StorcK CW, Wachsberger PR, Leeper DB, Berd D, Wahl ML, et al. Acute extracellular acidification increases nuclear associated protein levels in human melanoma cells during 42 °C hyperthermia and enhances cell killing. Int J Hyperthermia. 2002;18:404–15.

    Article  CAS  PubMed  Google Scholar 

  38. Burd R, Lavorgna SN, Daskalakis C, Wachsberger PR, Wahl ML, Biaglow JE, et al. Absence of Crabtree effect in human melanoma cells adapted to growth at low pH: reversal by respiratory inhibitors. Cancer Res. 2001;61:5630–5.

    CAS  PubMed  Google Scholar 

  39. Hasegawa T, Gu YH, Takahashi T, Hasegawa T, Yamamoto I. Enhancement of hyperthermic effects using rapid heating. In: Kosaka M, Sugahara T, Schmidt KL, Simon E, editors. Thermotherapy for neoplasia, inflammation, and pain. Tokyo: Springer Verlag; 2001. p. 439–44.

    Chapter  Google Scholar 

  40. Song CW, Park H, Griffin RJ. Improvement of tumor oxygenation by mild hyperthermia. Radiat Res. 2001;155:512–28.

    Article  Google Scholar 

  41. Song CW, Park HJ, Lee CK, Griffin R. Implications of increased tumour blood flow and oxygenation caused by mild temperature hyperthermia in tumor treatment. Int J Hyperthermia. 2005;21:761–7.

    Article  CAS  PubMed  Google Scholar 

  42. Brizel DM, Scully SP, Harrelson JM, Layfield LJ, Dodge RK, Charles HC. Radiation therapy and hyperthermia improve the oxygenation of human soft tissue sarcomas. Cancer Res. 1996;56:5347–50.

    CAS  PubMed  Google Scholar 

  43. Jones EL, Prosnitz LR, Dewhirst MW, Marcom PK, Hardenbergh H, Marks LB, et al. Thermochemoradiotherapy improves oxygenation in locally advanced breast cancer. Clin Cancer Res. 2004;10:4287–93.

    Article  CAS  PubMed  Google Scholar 

  44. Masunaga S, Nishimura Y, Hiraoka M, Abe M, Takahashi M, Ono K. Efficacy of mild temperature hyperthermia in combined treatments for cancer therapy. Thermal Med. 2007;23(3):103–12.

    Article  Google Scholar 

  45. Hall EJ, Giaccia AJ. Hyperthermia. In: Hall EJ, Giaccia AJ, editors. Radiobiology for the radiologist. 7th ed. Philadeiphia: Lippencott, Williams & Wilkins; 2012. p. 490–511.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Particle Radiation Biology, Division of Radiation Life Science, Research Reactor Institute, Kyoto University, 2-1010 Asashiro-nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan

    Shin-ichiro Masunaga

Authors
  1. Shin-ichiro Masunaga
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shin-ichiro Masunaga .

Editor information

Editors and Affiliations

  1. Kokura Lab, Health and Medical Sciences, Kyoto Gakuen University, Kyoto, Kyoto, Japan

    Satoshi Kokura

  2. Department of Inflammation and Immunolog, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan

    Toshikazu Yoshikawa

  3. Department of Radiation Oncology, Nara Medical University, Kashihara, Nara, Japan

    Takeo Ohnishi

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media Singapore

About this chapter

Cite this chapter

Masunaga, Si. (2016). Tumor Microenvironment and Hyperthermia. In: Kokura, S., Yoshikawa, T., Ohnishi, T. (eds) Hyperthermic Oncology from Bench to Bedside. Springer, Singapore. https://doi.org/10.1007/978-981-10-0719-4_14

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-0719-4_14

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-0717-0

  • Online ISBN: 978-981-10-0719-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation