Detection of Hypoxic Regions in the Bone Microenvironment

Guo, Wendi; Wu, Chia‐Lung

doi:10.1007/978-1-0716-1028-2_20

Cited by 1 publication

(2 citation statements)

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“…In case specific cell subpopulations have varying luciferase expression, this variation might be enhanced in special growth conditions (e.g. : exposure to hypoxia, composition of the tumor microenvironment [ 36 , 37 ]), where only a highly specialized subpopulation of DTCs might be able to survive and initiate metastatic growth. To this end, we could at least exclude variations in the percentages of Luciferase-positive tumor cells per metastasis in lung vs. bone (observational data only; representative images can be seen in Figs.…”

Section: Discussionmentioning

confidence: 99%

“…The use of luciferase mutants with bioluminescent properties that enable dual-color reporter assays has therefore been suggested [ 40 ]. Bone in particular has been considered a hypoxic environment [ 41 ] and might thus, in addition to hypoxic tumor regions, influence the obtained BLI signal intensity [ 37 , 42 , 43 ]. This could be another reason why the quantification of bone metastasis load by BLI is less accurate in bone compared to lung tissues.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of ex vivo bioluminescence imaging, Alu-qPCR and histology for the quantification of spontaneous lung and bone metastases in subcutaneous xenograft mouse models

Haider,

Freytag,

Krause

et al. 2024

Clin Exp Metastasis

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Bioluminescence imaging (BLI) is a non-invasive state-of-the-art-method for longitudinal tracking of tumor cells in mice. The technique is commonly used to determine bone metastatic burden in vivo and also suitable ex vivo to detect even smallest bone micro-metastases in spontaneous metastasis xenograft models. However, it is unclear to which extent ex vivo BLI correlates with alternative methods for metastasis quantification. Here, we compared ex vivo BLI, human DNA-based Alu-qPCR, and histology for the quantification of bone vs. lung metastases, which are amongst the most common sites of metastasis in prostate cancer (PCa) patients and spontaneous PCa xenograft models. Data from 93 immunodeficient mice were considered, each of which were subcutaneously injected with luciferase/RGB-labeled human PCa PC-3 cells. The primary tumors were resected at ~ 0.75 cm³ and mice were sacrificed ~ 3 weeks after surgery and immediately examined by ex vivo BLI. Afterwards, the right lungs and hind limbs with the higher BLI signal (BLIHi bone) were processed for histology, whereas the left lung lobes and hind limbs with the lower BLI signal (BLILo bone) were prepared for Alu-qPCR. Our data demonstrate remarkable differences in the correlation coefficients of the different methods for lung metastasis detection (r ~ 0.8) vs. bone metastasis detection (r ~ 0.4). However, the BLI values of the BLIHi and BLILo bones correlated very strongly (r ~ 0.9), indicating that the method per se was reliable under identical limitations; the overall level of metastasis to contralateral bones was astonishingly similar. Instead, the level of lung metastasis only weakly to moderately correlated with the level of bone metastasis formation. Summarized, we observed a considerable discrepancy between ex vivo BLI and histology/Alu-qPCR in the quantification of bone metastases, which was not observed in the case of lung metastases. Future studies using ex vivo BLI for bone metastasis quantification should combine multiple methods to accurately determine metastatic load in bone samples.

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Section: Discussionmentioning

confidence: 99%