Effects of radiation on the metastatic process

Sundahl, Nora; Duprez, Frédéric; Ost, Piet; Neve, Wilfried De; Mareel, Marcus

doi:10.1186/s10020-018-0015-8

Cited by 43 publications

(43 citation statements)

References 161 publications

(256 reference statements)

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“…Since metastasis is such a complex process involving a myriad of molecular mechanisms, it is unlikely that cancer cells that have been affected by irradiation-either directly or through bystander or abscopal effects-and survived would not exhibit some alterations in their metastatic ability. Indeed, there is considerable evidence for this in vitro and in pre-clinical studies [90] described below, and this may have implications for the development of radioresistance in tumours and consequent treatment failure. However, experimental results should be interpreted with caution as, clearly, in vitro and even in vivo models of cancer biology are not entirely reflective of the clinical situation and there is little convincing evidence that clinical use of radiotherapy to treat cancer results enhanced metastasis.…”

Section: Changes In Cancer Cell Metastatic Capacity Post-irradiationmentioning

confidence: 95%

Does Direct and Indirect Exposure to Ionising Radiation Influence the Metastatic Potential of Breast Cancer Cells

Kadhim

Mayah

Brooks

2020

Cancers

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Ionising radiation (IR) is commonly used for cancer therapy; however, its potential influence on the metastatic ability of surviving cancer cells exposed directly or indirectly to IR remains controversial. Metastasis is a multistep process by which the cancer cells dissociate from the initial site, invade, travel through the blood stream or lymphatic system, and colonise distant sites. This complex process has been reported to require cancer cells to undergo epithelial-mesenchymal transition (EMT) by which the cancer cells convert from an adhesive, epithelial to motile, mesenchymal form and is also associated with changes in glycosylation of cell surface proteins, which may be functionally involved in metastasis. In this paper, we give an overview of metastatic mechanisms and of the fundamentals of cancer-associated glycosylation changes. While not attempting a comprehensive review of this wide and fast moving field, we highlight some of the accumulating evidence from in vitro and in vivo models for increased metastatic potential in cancer cells that survive IR, focusing on angiogenesis, cancer cell motility, invasion, and EMT and glycosylation. We also explore the indirect effects in cells exposed to exosomes released from irradiated cells. The results of such studies need to be interpreted with caution and there remains limited evidence that radiotherapy enhances the metastatic capacity of cancers in a clinical setting and undoubtedly has a very positive clinical benefit. However, there is potential that this therapeutic benefit may ultimately be enhanced through a better understanding of the direct and indirect effects of IR on cancer cell behaviour.

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Section: Changes In Cancer Cell Metastatic Capacity Post-irradiationmentioning

confidence: 95%

Does Direct and Indirect Exposure to Ionising Radiation Influence the Metastatic Potential of Breast Cancer Cells

Kadhim

Mayah

Brooks

2020

Cancers

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“…In contrast, recent studies have suggested, but have not proven, that the application of ionizing radiation on tumor cells, the primary tumor, or the entire body could favor the metastatic process [13].…”

Section: Discussionmentioning

confidence: 94%

Multiple gingival metastasis of renal cell carcinoma: a case report

Boulanger

Gérard

Curien

2019

J Oral Med Oral Surg

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Introduction: Oral metastases are rare and represent only 1% of malignant diseases of the oral cavity, but they are often associated with poor prognosis. The primary tumor is recognizable in most cases; however, in 27.6% of cases, metastasis is the first clinical manifestation. Observation: An 82-year-old consulted for the recent appearance of a 1-cm-wide gingival tumor on 46. Since this patient had metastatic clear cell renal cell carcinoma, oral metastasis was confirmed by histopathology. In the following weeks, other oral metastases appeared. Palliative radiotherapy was the chosen treatment option, but the patient died before he could benefit from it. Discussion: Multiple oral metastases are rare, and metastasis of renal origin is not the most frequently encountered. The metastatic dissemination pathway described is hematogenous or lymphatic. Diagnosis is often easy if the primary tumor is already identified, but is a challenge if it is not, because the lesion often has a nonspecific appearance. Different surgical, radiotherapeutic, and medical therapeutic options exist, but are often palliative. A new immunotherapy route is under development and looks promising in the treatment of renal cell carcinoma. Conclusions: Oral metastasis often has poor prognosis, and management of the lesion is problematic. However, current research suggests a therapeutic and prognostic improvement.

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“…Exocytosis and vesicle secretion can further facilitate release of purinergic nucleotides, inflammatory molecules, enzymes, and ROS into the extracellular milieu, which collectively can alter the TME to become pro-tumorigenic (60,68,(80)(81)(82) [ Figure 5B]. The dose and time-dependence of radiation exposure can significantly alter the impact of RT on tumor microenvironment by affecting tumor or stromal cell behavior, migration, and treatment response (26,28,29,(83)(84)(85)(86)(87)(88)(89)(90). High-dose irradiation effects include hemorrhage, cognitive decline, neurodegeneration, and premature senescence, which can progress over time (91,92).…”

Section: Discussionmentioning

confidence: 99%

“…Metabolic alterations may be pro-tumorigenic, promoting glioma initiation and progression (21)(22)(23)(24). RT-induced metabolic changes in GBM depend on tumor volume, location, and dose-time regime of RT-administration, all of which can vary treatment response (8,(25)(26)(27)(28)(29). While differential metabolism of glioma tumor cells can be targeted to regress tumor growth, understanding the impact of radiation-induced metabolic alterations in GBM microenvironment can provide new avenues to maximize long term benefits of RT in GBM care.…”

Section: Introductionmentioning

confidence: 99%

Radiation Induced Metabolic Alterations Associate with Tumor Aggressiveness and Poor Outcome in Glioblastoma

Gupta

Vučković

Zhang

et al. 2020

Preprint

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AbstractGlioblastoma (GBM) is uniformly fatal with a one year median survival rate, despite the best available treatment, including radiotherapy (RT). Impacts of prior RT on tumor recurrence are poorly understood but may increase tumor aggressiveness. Metabolic changes have been investigated in radiation-induced brain injury; however, the tumor-promoting effect following prior radiation is lacking. Since RT is vital to GBM management, we quantified the tumor-promoting effects of prior radiotherapy (RT) on patient-derived intracranial GBM xenografts and characterized the metabolic alterations associated with the protumorigenic microenvironment. Human xenografts (GBM143) were implanted into nude mice 24h following 20Gy cranial radiation vs. sham animals. Tumors in pre-radiated mice were more proliferative and more infiltrative, yielding faster mortality (p<0.0001). Histologic evaluation of tumor associated macrophage/microglia (TAMs) revealed cells with a more fully activated ameboid morphology in pre-radiated animals. Microdialyzates from the radiated brain at the margin of tumor infiltration contralateral to the site of implantation were analyzed by unsupervised liquid chromatography-mass spectrometry (LC-MS). In pre-radiated animals, metabolites known to be associated with tumor progression (like, modified nucleotides and polyols) were identified. Whole-tissue metabolomic analysis of the pre-radiated brain microenvironment for metabolic alterations in a separate cohort of nude mice using 1H-NMR revealed significant decrease in levels of antioxidants (glutathione (GSH) and ascorbate (ASC)), NAD+, TCA intermediates, and increased ATP and GTP. Glutathione and ASC showed highest VIPpred (1.65) in OPLS-DA analysis. Involvement of ASC catabolism was further confirmed by GC-MS. To assess longevity of radiation effects, we compared survival with implantation occuring 2 months vs. 24h following radiation, finding worse survival in animals implanted at 2 months. These radiation-induced alterations are consistent with a chronic disease-like microenvironment characterized by reduced levels of antioxidants and NAD+, as well as elevated extracellular ATP and GTP serving as chemoattractants, promoting cell motility and vesicular secretion with decreased levels of GSH and ASC exacerbating oxidative stress. Taken together, these data suggest that IR induces tumor-permissive changes in the microenvironment with metabolomic alterations that may facilitate tumor aggressiveness with important implications for recurrent glioblastoma. Harnessing these metabolomic insights may provide opportunities to attenuate RT-associated aggressiveness of recurrent GBM.

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Effects of radiation on the metastatic process

Cited by 43 publications

References 161 publications

Does Direct and Indirect Exposure to Ionising Radiation Influence the Metastatic Potential of Breast Cancer Cells

Does Direct and Indirect Exposure to Ionising Radiation Influence the Metastatic Potential of Breast Cancer Cells

Multiple gingival metastasis of renal cell carcinoma: a case report

Radiation Induced Metabolic Alterations Associate with Tumor Aggressiveness and Poor Outcome in Glioblastoma

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