Radiation and the microenvironment – tumorigenesis and therapy

Barcellos‐Hoff, Mary Helen; Park, Catherine; Wright, Esmond

doi:10.1038/nrc1735

Cited by 453 publications

(397 citation statements)

References 83 publications

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“…Although radiotherapy is a major therapeutic modality for cancer treatment, previous findings indicate that irradiation promotes tumor migration, distant metastasis, and the invasive potential of cancer cells (6)(7)(8). Irradiation activates multiple signaling pathways (9) and affects the activity or abundance of proteases, growth factors, cytokines and adhesion proteins that are involved in tissue remodeling (10). The first major experiment examining the effect of local irradiation on the frequency of metastasis was performed by Kaplan and Murphy in 1949 (11).…”

Section: Introductionmentioning

confidence: 99%

Radiation induces epithelial-mesenchymal transition in colorectal cancer cells

Kawamoto

Yokoe²,

Tanaka³

et al. 2011

Oncol Rep

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Abstract. Radiotherapy remains a major approach to adjuvant therapy for patients with advanced rectal cancer. Nevertheless, the effects of radiation on malignant processes have yet to be clarified. The aim of this study was to assess the biological effects of radiation on colorectal cancer (CRC) cells with special reference to epithelial-mesenchymal transition (EMT), a key developmental program often activated during cancer invasion and metastasis. We investigated the effect of radiation on two colorectal cancer cell lines, CaR1 and DLD1, assessing cell morphology, motility, migration and invasive ability. Expression of molecules associated with EMT was determined using RT-PCR, Western blotting, and immunofluorescence staining in control and irradiated cells. We also used real-time RT-PCR to examine the expression of molecules associated with EMT before and after chemoradiotherapy. Thus, we studied 26 rectal cancer patients who received preoperative chemoradiotherapy followed by radical surgery. In addition, we examined the relationship between disease recurrence and the expression of a number of proteins. Irradiation caused CRC cells to undergo phenotypic changes characteristic of EMT: spindle-cell shape, loss of polarity, intercellular separation and pseudopodia formation. Irradiation enhanced cell migration and invasiveness. In irradiated CRC cells, molecular changes consistent with EMT were observed. In clinical samples, we observed molecular changes consistent with EMT, and those changes were significantly enhanced in patients with recurring disease. These results indicate that irradiation induces an alteration to a malignant phenotype consistent with EMT in colorectal cancer cells.

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Section: Introductionmentioning

confidence: 99%

Radiation induces epithelial-mesenchymal transition in colorectal cancer cells

Kawamoto

Yokoe²,

Tanaka³

et al. 2011

Oncol Rep

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“…Ionizing radiation exposure during total body irradiation has direct effects on irradiated cells and the microenvironment. 64 Radiation-induced injury can also contribute to secondary cell damage in the microenvironment as a consequence of an inflammatory-type response. 65 Transplantation of growth factor-dependant cells into syngeneic mice produces leukemia from donor cells in higher numbers and at a faster rate in irradiated compared with nonirradiated recipients.…”

Section: Seed and Soil Hypothesis As Applied To DCLmentioning

confidence: 99%

Donor cell leukemia: insight into cancer stem cells and the stem cell niche

Flynn

Kaufman

2006

Blood

127

108

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“…The interaction of ionizing irradiation (IR) with water is responsible for free radicals production including the highly reactive hydroxyl radical that can cause oxidatively damaged DNA (reviewed in Barcellos-Hoff et al 2 ). Therefore, it is possible that oxidatively damaged DNA which arises as a result of radiotherapy may be involved in the therapeutic effect of the IR and may be involved in the side effects.…”

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confidence: 99%

Small field radiotherapy of head and neck cancer patients is responsible for oxidatively damaged DNA/oxidative stress on the level of a whole organism

Roszkowski¹,

Gackowski

Różalski

et al. 2008

Intl Journal of Cancer

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It is possible that oxidatively damaged DNA which arises as a result of radiotherapy may be involved in the therapeutic effect of the ionizing radiation and in the side effects. Therefore, for the first time, the broad spectrum of oxidatively damaged DNA biomarkers: urinary excretion of 8-oxodG (8-oxo-7,8-dihydro-2 0 -deoxyguanosine), as well as the level of oxidatively damaged DNA in leukocytes, was analyzed in head and neck cancer patients (n 5 27) undergoing fractionated radiotherapy using methodologies which involve HPLC (high-performance liquid chromatography) prepurification followed by gas chromatography with isotope dilution mass spectrometry detection and HPLC/EC. Of all the analyzed parameters in the majority of patients, only urinary excretion of the modified nucleoside significantly increased over the initial level in the samples collected 24 hr after the last fraction. However, for the distinct subpopulation of 10 patients, a significant increase in the level of 8-oxodG in cellular DNA and a simultaneous drop in urinary 8-oxoGua (the repair product of oxidative DNA damage) were detected after completion of the therapy. Because 8-oxoGua is a repair product of the DNA damage, there is a possibility that, at least in the case of some patients with the lowest activity of OGG1 (8-oxo-7,8-dihydroguanine glycosylase), the combination of lower OGG1 repair efficacy and irradiation was associated with increased background level of 8-oxoGua in cellular DNA. Apparently reduced DNA repair is unable to cope with the radiation-induced, and the extra amount of 8-oxoGua leading to an increase of potentially mutagenic/carcinogenic lesions.

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Radiation and the microenvironment – tumorigenesis and therapy

Cited by 453 publications

References 83 publications

Radiation induces epithelial-mesenchymal transition in colorectal cancer cells

Radiation induces epithelial-mesenchymal transition in colorectal cancer cells

Donor cell leukemia: insight into cancer stem cells and the stem cell niche

Small field radiotherapy of head and neck cancer patients is responsible for oxidatively damaged DNA/oxidative stress on the level of a whole organism

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