A Rapid Histological Score for the Semiquantitative Assessment of Bone Metastases in Experimental Models of Breast Cancer

Neudert, Marcus; Fischer, Christian; Krempien, B.; Seibel, Markus J.; Bauss, Frieder

doi:10.1159/000151622

Cited by 4 publications

(5 citation statements)

References 12 publications

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“…In order to prove the utility of the new model, a set of human breast cancer cell lines were inoculated in the human breast implants, including the only breast cancer cell line SUM1315 which reported to be osteotropic in the hu-bone mouse model [24] and the most widely used but disputed osteotropic breast cancer cell line MDA-MB-231 [28][29][30][31]. SUM1315 was originally isolated from a xenografted metastatic nodule of a patient with invasive ductal carcinoma [32], while MDA-MB-231 was isolated from pleural effusion of a patient with disseminated disease relapsing several years after removal of the primary tumor [33].…”

Section: Discussionmentioning

confidence: 99%

Bone metastasis in a novel breast cancer mouse model containing human breast and human bone

Xia

Wang

Ding

et al. 2011

Breast Cancer Res Treat

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In practice, investigations for bone metastasis of breast cancer rely heavily on models in vivo. Lacking of such ideal model makes it difficult to study the whole process or accurate mechanism of each step of this metastatic disease. Development of xenograft mouse models has made great contributions in this area. Currently, the best animal model of breast cancer metastasizing to bone is NOD/SCID-hu models containing human bone, which makes it possible to let the breast cancer cells and the bone target of osteotropic metastasis be both of human origin. We have developed a novel mouse model containing both human bone and breast, and proved it functional and reliable. In this study, a set of human breast cancer cell line including MDA-MB-231, MDA-MB-231BO, MCF-7, ZR-75-1 and SUM1315 were characterized their osteotropism in this model. A specific cell line SUM1315 made species-specific bone metastasis, certifying the osteotropism-identification utility of the novel mouse model. Furthermore, gene expression and microRNA expression profiling analysis were done to the two SUM1315 derived sub lines isolated and purified from the orthotopic and metastatic xenograft. In addition, to demonstrate the disparity between the "spontaneous" and "forced" bone metastasis in mouse model, MDA-MB-231 cells were inoculated into both the human implants in this model simultaneously, and then primary cultured and profiling analyzed. Supported by overall results of profiling analyses, this study suggested the novel model was a useful tool for understanding, preventing and treating bone metastasis of breast cancer, meanwhile it had provided significant information for further investigations.

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Section: Discussionmentioning

confidence: 99%

Bone metastasis in a novel breast cancer mouse model containing human breast and human bone

Xia

Wang

Ding

et al. 2011

Breast Cancer Res Treat

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“…In intracardiac/tail-vein inoculated immunodeficient mouse models, these cells formed mouse bone metastases frequently, which initiated the use of these cells as an osteotropic cell line in many studies (14,20,21). Some studies, however, indicated that the method of injection influenced the metastatic tropism (7,14,(22)(23)(24).…”

Section: ------------------------------------------------------------mentioning

confidence: 99%

Human tissue-specific microenvironment: An essential requirement for mouse models of breast cancer

Xia

Wang²,

Yin³

et al. 2010

Oncol Rep

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Abstract. An ideal mouse model should closely mimic a clinical situation. However, for most models available, this is not the case since clinical trials frequently fail to reproduce the highly encouraging therapeutic results obtained from preclinical studies performed using mouse models. In this study, in the process of extending the application of our previously established breast tissue-derived orthotopic and metastatic (BOM) model, the human breast cancer cell line MDA-MB-231 failed to exhibit any osteotropic features that differed from previous studies. Our observations suggest that a human tissue-specific microenvironment could be an essential requirement for a successful mouse model of breast cancer. Here, multiple in vivo breast cancer models were used to confirm this hypothesis. Human breast tissue and cancellated bone were transplanted subcutaneously to female severe combined immunodeficiency disease (SCID) mice by different assemblies, to build several mouse models termed 'breast-breast', 'breastbone', 'bone-bone', 'MFP (mouse mammary fat pad)-bone', and 'MFP-breast' models. Two human breast cancer cell lines, MDA-MB-231 and MDA-MB-231BO, and the mouse breast cancer cell line TM40D were used. All cancer cells were labeled with GFP for gross observation. In addition, transplanted human tissues and various mouse tissues including bone, lung, liver, mesentery were examined microscopically. Based on morphological, immunohistochemical, and enzymohistochemical evidence obtained from several comparative experiments in 'breast-breast', 'breast-bone' and 'bone-bone' models, the BOM model was proved to be feasible and reliable. The organ tropism of the breast cancer cell line, which was derived from a mouse model by intracardiac inoculation in a pure mouse microenvironment, was reconsidered. The behavior of breast cancer cells in the mouse model was altered in response to the varying microenvironment. The results in this study suggest the human tissue-specific microenvironment is most likely an essential requirement in mouse models of breast cancer.

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“…Even as molecular biomarkers are playing a growing role, the scoring of stained specimens remains largely a visual and subjective process: Cells are coarsely scored as positive or negative or graded for degree of antigen staining, the percentage of positive cells is estimated visually, and overall scores are arbitrarily binned/scaled. This process requires considerable expertise and is susceptible to inter‐observer variability, despite standardization efforts 5–13 . The use of rough composite score scales (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…This process requires considerable expertise and is susceptible to inter-observer variability, despite standardization efforts. [5][6][7][8][9][10][11][12][13] The use of rough composite score scales (e.g. 0, 1+, 2+, 3+) is a tacit acknowledgement of the inherent imprecision and subjectivity involved.…”

mentioning

confidence: 99%

Cell-based quantification of molecular biomarkers in histopathology specimens

et al. 2011

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Aims To investigate the use of a computer-assisted technology for objective, cell-based quantification of molecular biomarkers in specified cell types in histopathology specimens, with the aim of advancing current visual estimation or pixel-level (rather than cell-based) quantification methods. Methods and results Tissue specimens were multiplex-immunostained to reveal cell structures, cell type markers, and analytes, and imaged with multispectral microscopy. The image data were processed with novel software that automatically delineates and types each cell in the field, measures morphological features, and quantifies analytes in different subcellular compartments of specified cells. The methodology was validated with the use of cell blocks composed of differentially labelled cultured cells mixed in known proportions, and evaluated on human breast carcinoma specimens for quantifying human epidermal growth factor receptor 2, oestrogen receptor, progesterone receptor, Ki67, phospho-extracellular signal-related kinase, and phospho-S6. Automated cell-level analyses closely matched human assessments, but, predictably, differed from pixel-level analyses of the same images. Conclusions Our method reveals the type, distribution, morphology and biomarker state of each cell in the field, and allows multiple biomarkers to be quantified over specified cell types, regardless of abundance. It is ideal for studying specimens from patients in clinical trials of targeted therapeutic agents, for investigating minority stromal cell subpopulations, and for phenotypic characterization to personalize therapy and prognosis.

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A Rapid Histological Score for the Semiquantitative Assessment of Bone Metastases in Experimental Models of Breast Cancer

Cited by 4 publications

References 12 publications

Bone metastasis in a novel breast cancer mouse model containing human breast and human bone

Bone metastasis in a novel breast cancer mouse model containing human breast and human bone

Human tissue-specific microenvironment: An essential requirement for mouse models of breast cancer

Cell-based quantification of molecular biomarkers in histopathology specimens

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