Human primary ductal carcinoma in situ (DCIS) subtype-specific pathology is preserved in a mouse intraductal (MIND) xenograft model.
Human primary ductal carcinoma in situ (DCIS) subtype-specific pathology is preserved in a mouse intraductal (MIND) xenograft model.
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DOI：
10.1002/path.2969
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发表时间：
2011-12
影响因子：
7.3
通讯作者：
Behbod, Fariba
中科院分区：
文献类型：
--
作者：
Valdez, Kelli Elizabeth;Fan, Fang;Smith, William;Allred, D. Craig;Medina, Daniel;Behbod, Fariba
导管原位癌（DCIS）是浸润性乳腺癌的非专性前兆。目前认识到DCIS病变表现出病变间和病变内的多样性，这表明演变为浸润性乳腺癌的过程比以前认识到的更复杂。在这里，我们证明了来自患者的手术和活检样本的小鼠导管内（MIND）模型的原代DCIS细胞的可重复生长。MIND涉及将细胞注射到NOD-SCID IL 2 R γ 1（NSG）小鼠乳腺导管中。将生物标志物表达和组织学异质的12份（8份独特和4份重复）DCIS和2份非典型增生标本注射到48只小鼠乳腺中，并分析成功的异种移植。总体而言，8周后，14/34和11/14的MIND异种移植腺体分别含有人DCIS和非典型增生细胞，这些细胞在导管内形成单层和多层上皮，并且在人细胞角蛋白、雌激素受体α（ER）和HER 2的表达方面是异质的。ER蛋白表达在MIND异种移植物中以类似于相应患者活检的比率重现。在患者活检和相应的MIND异种移植物中，HER 2蛋白表达和细胞核HER 2基因过表达仅限于DCIS病变，在周围基质或正常导管中未发现。异种移植的DCIS病变概括了人类疾病的病理学和异质性，从而为表征肿瘤间和肿瘤内异质性的独特细胞和分子基础以及DCIS至早期浸润性乳腺癌进展的过程提供了有力的工具。
Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer. The current recognition that DCIS lesions exhibit inter- and intra-lesion diversity suggests that the process of evolution to invasive breast cancer is more complex than previously recognized. Here we demonstrate the reproducible growth of primary DCIS cells derived from patient’s surgical and biopsy samples by the mouse intraductal (MIND) model. MIND involves injection of cells into the NOD-SCID IL2Rgammanull (NSG) mouse mammary ducts. Twelve (8 unique and 4 repeats) DCIS and 2 atypical hyperplasia specimens, heterogeneous with respect to biomarker expression and histology, were injected into 48 mouse mammary glands and analyzed for successful xenotransplantation. Overall, 14/34 and 11/14 of MIND xenotransplanted glands contained human DCIS and atypical hyperplastic cells, respectively, after 8 weeks, which formed single and multi-layered epithelium inside the ducts, and were heterogeneous with respect to expression of human cytokeratins, estrogen receptor α (ER), and HER2. ER protein expression was recapitulated in MIND xenografts at ratios similar to the corresponding patient biopsies. In both patient biopsies and corresponding MIND xenografts HER2 protein expression and nuclear HER2 gene over-expression was restricted to the DCIS lesions and were not found in the surrounding stroma or normal ducts. The xenografted DCIS lesions recapitulate the pathology and heterogeneity of human disease thus providing a powerful tool for the characterization of the distinct cellular and molecular basis of inter- and intra-tumoral heterogeneity and the processes of DCIS to early invasive breast cancer progression.
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影响因子：
7.3
作者：
Bombonati, Alessandro;Sgroi, Dennis C.
通讯作者：
Sgroi, Dennis C.
影响因子：
2.5
作者：
Miller, FR
通讯作者：
Miller, FR
影响因子：
2.5
作者：
Boland, GP;Knox, WF;Bundred, NJ
通讯作者：
Bundred, NJ
影响因子：
8
作者：
Schulze-Garg, C;Löhler, J;Deppert, W
通讯作者：
Deppert, W
影响因子：
2.5
作者：
Gudjonsson, Thorarinn;Adriance, Melissa C.;Bissell, Mina J.
通讯作者：
Bissell, Mina J.