New bone formation and osteolysis by a metastatic, highly invasive canine prostate carcinoma xenograft

LeRoy, Bruce E.; Thudi, Nanda K.; Nadella, Murali V.P.; Toribio, Ramiro E.; Tannehill-Gregg, Sarah H.; Bokhoven, Adrie van; Davis, Deborah; Corn, Stephanie; Rosol, Thomas J.

doi:10.1002/pros.20408

Cited by 65 publications

(84 citation statements)

References 23 publications

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“…Osteoblastic metastases tend to induce new woven bone on the surface of pre-existing medullary trabecular bone [15], which was observed in our model, both in untreated and in PDT-treated groups. Similar observations of overwhelming osteolysis in addition to definite areas of new bone formation have also been described in mouse models of mixed osteolytic/osteoblastic metastases [12,[16][17][18]. As such, it remains important to consider host bony repair mechanisms when considering the effect of tumor invasion of vertebrae bone.…”

Section: Discussionmentioning

confidence: 72%

“…Canine Ace-1 prostate cancer cells previously transfected with the luciferase gene to enable in vivo bioluminescent image monitoring of tumor growth were utilized [12]. Ace-1/Luc?…”

Section: In Vivo Tumor Modelmentioning

confidence: 99%

“…With increasing observations of these mixed osteolytic/osteoblastic lesions secondary to breast cancer, the evaluation of PDT on a more clinically representative preclinical model is necessary. Ace-1 canine prostate cancer cells have been shown to induce well-defined osteolytic/osteoblastic skeletal metastases in mice [12]. The objective of this study was to evaluate the effects of PDT on tumor burden and bone quality in a preclinical rat model of mixed osteolytic/ osteoblastic spinal metastases.…”

Section: Introductionmentioning

confidence: 99%

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Local treatment of mixed osteolytic/osteoblastic spinal metastases: is photodynamic therapy effective?

Wise-Milestone

Akens

et al. 2011

Breast Cancer Res Treat

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The widespread use of systemic and local therapies aimed at spinal metastatic lesions secondary to breast cancer has increased the incidence of mixed osteolytic/osteoblastic patterns of bony disease. The complex structure of these lesions requires novel therapeutic approaches to both reduce tumor burden and restore structural stability. In photodynamic therapy (PDT), a minimally invasive approach can be used to employ light to activate a photosensitizing agent that preferentially accumulates in tumor tissue, leading to cell toxicity and death. Previous work in an osteolytic rat model (MT-1) demonstrated that PDT effectively ablates tumor and improves vertebral structural properties. The aim of this study was to assess the efficacy of PDT in a rat model of mixed osteolytic/osteoblastic spinal metastases. Mixed spinal metastases were generated through intracardiac injection of Ace-1 canine prostate cancer cells into female athymic rats (day 0). A single PDT treatment was applied to lumbar vertebra L2 of tumor-bearing and healthy control rats (day 14). PDT-treated and untreated control rats were euthanized and excised spines imaged with μCT to assess bone quality (day 21). Spines were mechanically tested or histologically processed to assess mechanical integrity, tumor burden, and remodelling properties. Untreated tumor-bearing vertebrae showed large areas of osteolysis and areas of immature, new bone formation. The overall bone quality resulting from these lesions consisted of decreased structural properties but without a significant reduction in mechanical integrity. PDT was shown to significantly decrease tumor burden and osteoclastic activity, thereby improving vertebral bone structural properties. While non-tumor-bearing vertebrae exhibited significantly more new bone formation following PDT, the already heightened level of new bone formation in the mixed tumor-bearing vertebrae was not further increased. As such, the effect of PDT on mixed metastases may be more influenced by suppression of osteoclastic resorption as opposed to the triggering of new bone formation.

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Section: Discussionmentioning

confidence: 72%

“…Canine Ace-1 prostate cancer cells previously transfected with the luciferase gene to enable in vivo bioluminescent image monitoring of tumor growth were utilized [12]. Ace-1/Luc?…”

Section: In Vivo Tumor Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Local treatment of mixed osteolytic/osteoblastic spinal metastases: is photodynamic therapy effective?

Wise-Milestone

Akens

et al. 2011

Breast Cancer Res Treat

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“…Osteolytic and mixed lesions were developed via intracardiac injection of MT1 human breast cancer cells, and Ace-1 canine prostate cancer cells, respectively (Burch et al, 2007;LeRoy et al, 2006). Three weeks post injection the presence of vertebral metastases was confirmed via bioluminescent imaging, prior to sacrifice.…”

Section: Animal Modelmentioning

confidence: 99%

Can micro-imaging based analysis methods quantify structural integrity of rat vertebrae with and without metastatic involvement?

Hojjat

Beek

Akens

et al. 2012

Journal of Biomechanics

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This study compares the ability of μCT image-based registration, 2D structural rigidity analyses and multimodal continuum-level finite element (FE) modeling in evaluating the mechanical stability of healthy, osteolytic, and mixed osteolytic/osteoblastic metastatically involved rat vertebrae. μMR and μCT images (loaded and unloaded) were acquired of lumbar spinal motion segments from 15rnu/rnu rats (five per group). Strains were calculated based on image registration of the loaded and unloaded μCT images and via analysis of FE models created from the μCT and μMR data. Predicted yield load was also calculated through 2D structural rigidity analysis of the axial unloaded μCT slices. Measures from the three techniques were compared to experimental yield loads. The ability of these methods to predict experimental yield loads were evaluated and image registration and FE calculated strains were directly compared. Quantitatively for all samples, only limited weak correlations were found between the image-based measures and experimental yield load. In comparison to the experimental yield load, we observed a trend toward a weak negative correlation with median strain calculated using the image-based strain measurement algorithm (r=-0.405, p=0.067), weak significant correlations (p<0.05) with FE based median and 10th percentile strain values (r=-0.454, -0.637, respectively), and a trend toward a weak significant correlation with FE based mean strain (r=-0.366, p=0.09). Individual group analyses, however, yielded more and stronger correlations with experimental results. Considering the image-based strain measurement algorithm we observed moderate significant correlations with experimental yield load (p<0.05) in the osteolytic group for mean and median strain values (r=-0.840, -0.832, respectively), and in the healthy group for median strain values (r=-0.809). Considering the rigidity-based predicted yield load, we observed a strong significant correlation with the experimental yield load in the mixed osteolytic/osteoblastic group (r=0.946) and trend toward a moderate correlation with the experimental yield load in the osteolytic group (r=0.788). Qualitatively, strain patterns in the vertebral bodies generated using image registration and FEA were well matched, yet quantitatively a significant correlation was found only between mean strains in the healthy group (r=0.934). Large structural differences in metastatic vertebrae and the complexity of motion segment loading may have led to varied modes of failure. Improvements in load characterization, material properties assignments and resolution are necessary to yield a more generalized ability for image-based registration, structural rigidity and FE methods to accurately represent stability in healthy and pathologic scenarios.

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“…The ACE-1 cell line, derived from a spontaneous dog prostate carcinoma 47 , forms osteoblastic bone metastases in athymic nude mice 30,90,91 . Prostate cancer cells were passaged every 3–4 days, and were harvested for cancer cell injection between 6 and 10 passages after thaw.…”

Section: Methodsmentioning

confidence: 99%

Targeting cells of the myeloid lineage attenuates pain and disease progression in a prostate model of bone cancer

Thompson

Jiménez-Andrade

Chartier

et al. 2015

Pain

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New bone formation and osteolysis by a metastatic, highly invasive canine prostate carcinoma xenograft

Abstract: The Ace-1 xenograft is a useful model for investigating the pathogenesis of prostate cancer invasion and mixed osteoblastic/osteolytic bone metastases.

Cited by 65 publications

References 23 publications

Local treatment of mixed osteolytic/osteoblastic spinal metastases: is photodynamic therapy effective?

Local treatment of mixed osteolytic/osteoblastic spinal metastases: is photodynamic therapy effective?

Can micro-imaging based analysis methods quantify structural integrity of rat vertebrae with and without metastatic involvement?

Targeting cells of the myeloid lineage attenuates pain and disease progression in a prostate model of bone cancer

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