Experimental manipulation of radiographic density in mouse mammary gland

Hariri, Mehrdad; Wood, Geoffrey A.; DiGrappa, Marco A; MacPherson, Michelle; Backman, Stéphanie A.; Yaffe, Martin J.; Mak, Tak W.; Boyd, Norman F.; Khokha, Rama

doi:10.1186/bcr901

Cited by 7 publications

(13 citation statements)

References 27 publications

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“…A robust animal model for studying MD in vivo may ultimately clarify this. Harari et al investigated the radiographic density and histology of murine MFPs deficient in epithelial structure, and containing hyperplastic or malignant epithelium [14]. Digitized images of MFP whole mounts, with epithelial mass and breast density measurement using computer-aided thresholding has been described [27].…”

Section: Few Existing Models Of MDmentioning

confidence: 99%

“…Currently, there are few suitable animal models in which to study MD. While radiological examination of mouse mammary fat pads (MFPs) in vivo and ex vivo has been described [14], quantification of MFP radiographic density is yet to be established. Here we describe an in vivo biochamber xenograft system in xenograft SCID mice as a model of human MD.…”

Section: Introductionmentioning

confidence: 99%

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High and low mammographic density human breast tissues maintain histological differential in murine tissue engineering chambers

Chew

Huang

Lin

et al. 2012

Breast Cancer Res Treat

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Mammographic density (MD) is the area of breast tissue that appears radiologically white on mammography. Although high MD is a strong risk factor for breast cancer, independent of BRCA1/2 mutation status, the molecular basis of high MD and its associated breast cancer risk is poorly understood. MD studies will benefit from an animal model, where hormonal, gene and drug perturbations on MD can be measured in a preclinical context. High and low MD tissues were selectively sampled by stereotactic biopsy from operative specimens of high-risk women undergoing prophylactic mastectomy. The high and low MD tissues were transferred into separate vascularised biochambers in the groins of SCID mice. Chamber material was harvested after 6 weeks for histological analyses and immunohistochemistry for cytokeratins, vimentin and a human-specific mitochondrial antigen. Within-individual analysis was performed in replicate mice, eliminating confounding by age, body mass index and process-related factors, and comparisons were made to the parental human tissue. Maintenance of differential MD post-propagation was assessed radiographically. Immunohistochemical staining confirmed the preservation of human glandular and stromal components in the murine biochambers, with maintenance of radiographic MD differential. Propagated high MD regions had higher stromal (p = 0.0002) and lower adipose (p = 0.0006) composition, reflecting the findings in the original human breast tissue, although glands appeared small and non-complex in both high and low MD groups. No significant differences were observed in glandular area (p = 0.4) or count (p = 0.4) between high and low MD biochamber tissues. Human mammary glandular and stromal tissues were viably maintained in murine biochambers, with preservation of differential radiographic density and histological features. Our study provides a murine model for future studies into the biomolecular basis of MD as a risk factor for breast cancer.

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Section: Few Existing Models Of MDmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High and low mammographic density human breast tissues maintain histological differential in murine tissue engineering chambers

Chew

Huang

Lin

et al. 2012

Breast Cancer Res Treat

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“…If so, then possible longer-term therapeutic strategies might emerge. It will be important to recapitulate raised breast MD in mouse models, thereby enabling the role of mechano-sensitive signalling to be tested [ 75 ]. SCID mice might also provide new opportunities for growing human low and high MD breast samples, enabling an exploration of density-signalling mechanisms and therapeutic pathways to reverse it [ 76 ].…”

Section: Introductionmentioning

confidence: 99%

Raised mammographic density: causative mechanisms and biological consequences

2016

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High mammographic density is the most important risk factor for breast cancer, after ageing. However, the composition, architecture, and mechanical properties of high X-ray density soft tissues, and the causative mechanisms resulting in different mammographic densities, are not well described. Moreover, it is not known how high breast density leads to increased susceptibility for cancer, or the extent to which it causes the genomic changes that characterise the disease. An understanding of these principals may lead to new diagnostic tools and therapeutic interventions.

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“…4c,d) due to the elevated mammary tissue density of PyMT mice masking the detection of µcals [20]. The elevated radiographic density of PyMT mice was previously shown to be due to hyperplastic epithelium and greater amounts of collagen at a premalignant stage of development [20,36,37], which recapitulated elevated radiographic density in human breast tissue associated with fibroglandular tissue. Importantly, the addition of engineered µcals within wildtype and PyMT mice was further able to recapitulate the clinical challenges of detecting small abnormalities in dense breast tissue by radiographic imaging.…”

Section: Binding Affinity To Hamentioning

confidence: 85%

Effects of bisphosphonate ligands and PEGylation on targeted delivery of gold nanoparticles for contrast-enhanced radiographic detection of breast microcalcifications

et al. 2018

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Experimental manipulation of radiographic density in mouse mammary gland

Abstract: Introduction Extensive mammographic density in women is associated with increased risk for breast cancer. Mouse models provide a powerful approach to the study of human diseases, but there is currently no model that is suited to the study of mammographic density.

Cited by 7 publications

References 27 publications

High and low mammographic density human breast tissues maintain histological differential in murine tissue engineering chambers

High and low mammographic density human breast tissues maintain histological differential in murine tissue engineering chambers

Raised mammographic density: causative mechanisms and biological consequences

Effects of bisphosphonate ligands and PEGylation on targeted delivery of gold nanoparticles for contrast-enhanced radiographic detection of breast microcalcifications

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