An intraductal human-in-mouse transplantation model mimics the subtypes of ductal carcinoma in situ.
An intraductal human-in-mouse transplantation model mimics the subtypes of ductal carcinoma in situ.
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DOI：
10.1186/bcr2358
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Medina D
中科院分区：
文献类型：
--
作者：
Behbod F;Kittrell FS;LaMarca H;Edwards D;Kerbawy S;Heestand JC;Young E;Mukhopadhyay P;Yeh HW;Allred DC;Hu M;Polyak K;Rosen JM;Medina D
非侵袭性乳腺肿瘤的人类模型是有限的，现有的体内模型不能模拟肿瘤间和肿瘤内的异质性。导管原位癌（DCIS）是最常见的类型（80%）的非侵袭性乳腺病变。本研究的目的是开发一种体内模型，从而可以复制和研究人类DCIS的自然进展。为了实现这一目标，开发了导管内人鼠（HIM）移植模型。由此产生的模型模拟了体内人类非侵袭性乳腺癌的一些多样性，用于显示人类DCIS的亚型是否可能包含不同的肿瘤起始细胞亚群。通过将人DCIS细胞系（MCF10DCIS.COM和SUM-225）以及来源于原代人DCIS的细胞（FSK-H7）经裂开的乳头直接注射到原代小鼠乳腺导管中，建立了导管内模型。注射后6 - 8周，进行整体包埋、苏木精-伊红和免疫荧光染色，以评估DCIS样病变生长的类型和程度。为了鉴定肿瘤起始细胞，用流式细胞术从MCF10DCIS.COM和SUM-225中分选推定的人乳腺干/祖细胞亚群，并用Fisher精确检验比较它们的体内生长分数。人DCIS细胞最初在乳腺导管内生长，随后在某些情况下进展为侵入基质。病变在组织学上与临床人类DCIS几乎相同。该方法成功用于培养DCIS细胞系（MCF10DCIS.COM和SUM-225）以及原代人DCIS（FSK-H7）。MCF10DCIS.COM代表基底样DCIS模型，而SUM-225和FSK-H7细胞是HER-2+ DCIS的模型。通过这种方法，我们发现人类DCIS的各种亚型似乎包含不同的肿瘤起始细胞亚群。导管内HIM移植模型提供了一个宝贵的工具，模仿人类乳腺异质性的非侵入性阶段，并允许研究乳腺癌进展的不同分子和细胞机制。
Human models of noninvasive breast tumors are limited, and the existing in vivo models do not mimic inter- and intratumoral heterogeneity. Ductal carcinoma in situ (DCIS) is the most common type (80%) of noninvasive breast lesions. The aim of this study was to develop an in vivo model whereby the natural progression of human DCIS might be reproduced and studied. To accomplish this goal, the intraductal human-in-mouse (HIM) transplantation model was developed. The resulting models, which mimicked some of the diversity of human noninvasive breast cancers in vivo, were used to show whether subtypes of human DCIS might contain distinct subpopulations of tumor-initiating cells. The intraductal models were established by injection of human DCIS cell lines (MCF10DCIS.COM and SUM-225), as well as cells derived from a primary human DCIS (FSK-H7), directly into the primary mouse mammary ducts via cleaved nipple. Six to eight weeks after injections, whole-mount, hematoxylin and eosin, and immunofluorescence staining were performed to evaluate the type and extent of growth of the DCIS-like lesions. To identify tumor-initiating cells, putative human breast stem/progenitor subpopulations were sorted from MCF10DCIS.COM and SUM-225 with flow cytometry, and their in vivo growth fractions were compared with the Fisher's Exact test. Human DCIS cells initially grew within the mammary ducts, followed by progression to invasion in some cases into the stroma. The lesions were histologically almost identical to those of clinical human DCIS. This method was successful for growing DCIS cell lines (MCF10DCIS.COM and SUM-225) as well as a primary human DCIS (FSK-H7). MCF10DCIS.COM represented a basal-like DCIS model, whereas SUM-225 and FSK-H7 cells were models for HER-2+ DCIS. With this approach, we showed that various subtypes of human DCIS appeared to contain distinct subpopulations of tumor-initiating cells. The intraductal HIM transplantation model provides an invaluable tool that mimics human breast heterogeneity at the noninvasive stages and allows the study of the distinct molecular and cellular mechanisms of breast cancer progression.
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影响因子：
2.5
作者：
Miller, FR
通讯作者：
Miller, FR
影响因子：
7.5
作者：
Livasy, CA;Karaca, G;Perou, CM
通讯作者：
Perou, CM
影响因子：
11.5
作者：
Allred, D. Craig;Wu, Yun;Medina, Dan
通讯作者：
Medina, Dan
在人异种移植模型以及乳腺癌和卵巢癌细胞的体外和体内，Farnesyl转移酶抑制剂（R115777）对导管癌的原位导管癌的影响。
影响因子：
7.4
作者：
Wärnberg, F;White, D;Anderson, E;Knox, F;Clarke, RB;Morris, J;Bundred, NJ
通讯作者：
Bundred, NJ
影响因子：
11.5
作者：
Nielsen, TO;Hsu, FD;Perou, CM
通讯作者：
Perou, CM