Understanding hypoxia microenvironment of micrometastases

Li, Xiaofeng; Ma, Yuanyuan; Jiang, Huijie

doi:10.5430/jst.v2n2p28

Cited by 5 publications

(4 citation statements)

References 45 publications

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“…18 F-FDG PET-CT scans based on the Warburg effect has been widely used for cancer detection and therapy response [23] , [24] , [25] . The success of such utilization is not surprising, because most solid malignancies have increased 18 F-FDG, as hypoxia is a feature of most solid cancers [26] , [27] , [28] , [29] , [30] , [31] . However, it is also likely that the presence of associated low 18 F-FDG activities of some tumors or tumor regions [10] , [11] is probably due to a lack of hypoxia in such tumors or regions of the tumors.…”

Section: Discussionmentioning

confidence: 99%

18F-Fluorodeoxyglucose Uptake and Tumor Hypoxia: Revisit 18F-Fluorodeoxyglucose in Oncology Application

et al. 2014

Translational Oncology

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This study revisited 18F-fluorodeoxyglucose (18F-FDG) uptake and its relationship to hypoxia in various tumor models. METHODS: We generated peritoneal carcinomatosis and subcutaneous xenografts of colorectal cancer HT29, breast cancer MDA-MB-231, and non–small cell lung cancer A549 cell lines in nude mice. The partial oxygen pressure (pO2) of ascites fluid was measured. 18F-FDG accumulation detected by digital autoradiography was related to tumor hypoxia visualized by pimonidazole binding and glucose transporter-1 (GLUT-1) in frozen tumor sections. RESULTS: Ascites pO2 was 0.90 ± 0.53 mm Hg. Single cancer cells and clusters suspended in ascites fluid as well as submillimeter serosal tumors stained positive for pimonidazole and GLUT-1 and had high 18F-FDG uptake. In contrast, 18F-FDG uptake was significantly lower in normoxic portion (little pimonidazole binding or GLUT-1 expression) of larger serosal tumors or subcutaneous xenografts, which was not statistically different from that in the liver. CONCLUSIONS: Glucose demand (18F-FDG uptake) in severely hypoxic ascites carcinomas and hypoxic portion of larger tumors is significantly higher than in normoxic cancer cells. Warburg effect originally obtained from Ehrlich ascites carcinoma may not apply to normoxic cancer cells. Our findings may benefit the better understanding of 18F-FDG PET in oncology application.

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Section: Discussionmentioning

confidence: 99%

18F-Fluorodeoxyglucose Uptake and Tumor Hypoxia: Revisit 18F-Fluorodeoxyglucose in Oncology Application

et al. 2014

Translational Oncology

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“…Since well-oxygenated, proliferating cancer cells can be targeted by chemo-, radio-and immunotherapies, our metabolic regimen is a natural candidate for combination with these therapies for synergistic therapeutic effects. Additionally, since tumor micrometastases are also hypoxic [5,18,21], lowering systemic glucose may affect tumor metastasis similarly to affecting the primary tumor (see Supplementary Materials), increasing the regimen's potential. Finally, this metabolic regimen may be similarly effective against a broad range of other FDG-PET-positive (glycolytic) tumors in other organs [10,18,71].…”

Section: Discussionmentioning

confidence: 99%

“…Aggressively growing tumors develop hypoxic microenvironments due to insufficient and haphazard tumor vascularization [1][2][3]. Chronic tumor hypoxia promotes metastasis [4,5], increases angiogenesis [6,7], inhibits the immune response [8,9] and interferes with apoptosis [10]. Furthermore, tumor-derived micrometastases are initially avascular and, therefore, exist in a state of acute hypoxia [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

The combined treatment with ketogenic diet and metformin slows tumor growth in two mouse models of triple negative breast cancer

Schmidt,

Thatcher,

Grobe

et al. 2024

transl med commun

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Background Many tumors contain hypoxic microenvironments caused by inefficient tumor vascularization. Hypoxic tumors have been shown to resist conventional cancer therapies. Hypoxic cancer cells rely on glucose to meet their energetic and anabolic needs to fuel uncontrolled proliferation and metastasis. This glucose dependency is linked to a metabolic shift in response to hypoxic conditions. Methods To leverage the glucose dependency of hypoxic tumor cells, we assessed the effects of a mild reduction in systemic glucose by controlling both dietary carbohydrates with a ketogenic diet and endogenous glucose production by using metformin on two mouse models of triple-negative breast cancer (TNBC). Results Here, we showed that animals with TNBC treated with the combination regimen of ketogenic diet and metformin (a) had their tumor burden lowered by two-thirds, (b) displayed 38% slower tumor growth, and (c) showed 36% longer latency, compared to the animals treated with a ketogenic diet or metformin alone. As a result, lowering systemic glucose by this combined dietary and pharmacologic approach improved overall survival in our mouse TNBC models by 31 days, approximately equivalent to 3 years of life extension in human terms. Conclusion This preclinical study demonstrates that reducing systemic glucose by combining a ketogenic diet and metformin significantly inhibits tumor proliferation and increases overall survival. Our findings suggest a possible treatment for a broad range of hypoxic and glycolytic tumor types that can augment existing treatment options to improve patient outcomes.

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“…Metastatic disease especially micrometastasis is highly hypoxia. Thus, in recent years, cancer researches have begun to focus on the changes in the tumor microenvironment of micrometastasis [ 53 ]. Huang et al compared the uptake of 18 F-FMISO with the hypoxia-staining marker pimonidazole in subcutaneous xenograft and peritoneal metastases generated by non-small cell lung cancer cell lines (A549 and HTB177), and found significant overlap between the two markers [ 6 ].…”

Section: Application Of 18 F-fmiso Petmentioning

confidence: 99%

18F-Fluoromisonidazole in tumor hypoxia imaging

Zou

et al. 2017

Oncotarget

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Hypoxia is a common feature of solid tumors that is closely associated with radiotherapy and chemotherapy resistance, metastasis and tumors prognosis. Thus, it is important to assess hypoxia in tumors for estimating prognosis and selecting appropriate treatment procedures. 18F-Fluoromisonidazole positron emission tomography (18F-FMISO PET) has been widely used to visualize tumor hypoxia in a comprehensive and noninvasive way, both in the clinical and preclinical settings. Here we review the concept, mechanisms and detection methods of tumor hypoxia. Furthermore, we discuss the correlation between 18F-FMISO PET and other detection methods, current applications of 18F-FMISO PET and the development prospects of this imaging technology.

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Understanding hypoxia microenvironment of micrometastases

Cited by 5 publications

References 45 publications

18F-Fluorodeoxyglucose Uptake and Tumor Hypoxia: Revisit 18F-Fluorodeoxyglucose in Oncology Application

18F-Fluorodeoxyglucose Uptake and Tumor Hypoxia: Revisit 18F-Fluorodeoxyglucose in Oncology Application

The combined treatment with ketogenic diet and metformin slows tumor growth in two mouse models of triple negative breast cancer

18F-Fluoromisonidazole in tumor hypoxia imaging

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