Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jun;53(6):1029-1035.
doi: 10.1038/s12276-021-00640-9. Epub 2021 Jun 16.

Tumor microenvironment and radioresistance

Tatsuya Suwa  1   2   3 , Minoru Kobayashi  1   2 , Jin-Min Nam  1   2 , Hiroshi Harada  4   5
Affiliations
Review

Tumor microenvironment and radioresistance

Tatsuya Suwa et al. Exp Mol Med. 2021 Jun.

Abstract

Metastasis is not the result of a random event, as cancer cells can sustain and proliferate actively only in a suitable tissue microenvironment and then form metastases. Since Dr. Stephen Paget in the United Kingdom proposed the seed and soil hypothesis of cancer metastasis based on the analogy that plant seeds germinate and grow only in appropriate soil, considerable attention has focused on both extracellular environmental factors that affect the growth of cancer cells and the tissue structure that influences the microenvironment. Malignant tumor tissues consist of not only cancer cells but also a wide variety of other cells responsible for the inflammatory response, formation of blood vessels, immune response, and support of the tumor tissue architecture, forming a complex cellular society. It is also known that the amounts of oxygen and nutrients supplied to each cell differ depending on the distance from tumor blood vessels in tumor tissue. Here, we provide an overview of the tumor microenvironment and characteristics of tumor tissues, both of which affect the malignant phenotypes and radioresistance of cancer cells, focusing on the following keywords: diversity of oxygen and nutrient microenvironment in tumor tissue, inflammation, immunity, and tumor vasculature.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Schematic diagram of microenvironments in and among tumor cords.
Because of the limited distance that molecular oxygen diffuses from functional tumor blood vessels, pO2 gradually decreases according to the distance from the vessel, leading to the generation of chronically hypoxic and necrotic regions. The availability of nutrients, such as glucose, and the pH are relatively low in these regions.
Fig. 2
Fig. 2. Radioresistance of cells induced by UCHL1-HIF-1 pathway-dependent reprogramming of the carbohydrate metabolic pathway.
HIF-1 mediates reprogramming of the glucose metabolic pathway from mitochondrial oxidative phosphorylation to glycolysis. UCHL1 causes radioresistance by inducing HIF-1-mediated reprogramming and a resulting increase in the intracellular level of GSH in a PPP-dependent manner.
Fig. 3
Fig. 3. Crosstalk between cancer cells and TAMs or CAFs in tumor tissue.
Crosstalk between cancer cells and TAMs or CAFs is regulated by the indicated factors.
See this image and copyright information in PMC

References

    1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–674. - PubMed
    1. Harada H. How can we overcome tumor hypoxia in radiation therapy? J. Radiat. Res. 2011;52:545–556. - PubMed
    1. Yeom CJ, Goto Y, Zhu Y, Hiraoka M, Harada H. Microenvironments and cellular characteristics in the micro tumor cords of malignant solid tumors. Int. J. Mol. Sci. 2012;13:13949–13965. - PMC - PubMed
    1. Vaupel P. Tumor microenvironmental physiology and its implications for radiation oncology. Semin. Radiat. Oncol. 2004;14:198–206. - PubMed
    1. Brown JM. Evidence for acutely hypoxic cells in mouse tumours, and a possible mechanism of reoxygenation. Br. J. Radio. 1979;52:650–656. - PubMed

Publication types