CHARACTERIZATION OF BRAIN AND BONE-METASTASIZING CLONES SELECTED FROM AN ETHYLNITROSOUREA-INDUCED RAT MAMMARY-CARCINOMA

CHARACTERIZATION OF BRAIN AND BONE-METASTASIZING CLONES SELECTED FROM AN ETHYLNITROSOUREA-INDUCED RAT MAMMARY-CARCINOMA
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DOI:
10.1007/bf01753835
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发表时间:
1994-07-01
影响因子:
4
通讯作者:
STOICA, G
STOICA, G
中科院分区:
医学3区
文献类型:
--
作者:
HALL, DG;STOICA, G

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使用ENU 1564开发了乳腺癌、脑和骨转移的动物模型,ENU 1564是从由N-乙基-N-亚硝基脲诱导的雌性Berlin-Druckrey IV大鼠中的转移性乳腺癌建立的细胞系。原始肿瘤分离株(命名为FP 1)在原位接种到乳腺脂肪垫(mfp)后自发转移到局部淋巴结和肺,并在左心室(LV)接种后广泛转移。从FP 1中,从脑转移瘤(命名为Br 7-C5)或从体外缓慢生长的集落(FP 2-A11)中选择两个亚系,然后克隆并在自发和实验转移测定中进行比较。将10(5)个细胞接种到mfp中后,Br 7-C5在接种部位形成大肿瘤(9.4 +/-3.3g),并在接种后55天(dpi)自发转移到肺和淋巴结。相比之下,FP 2-A11在mfp内产生小得多的肿瘤(0.6 +/-0.3g),并且在55 dpi时未能转移。通过LV接种10(4)个Br 7-C5细胞的大鼠在24 +/- 1.4 dpi时出现体重减轻、头倾斜和呼吸困难的体征,并在脑、骨、肺、心脏、肾脏和胃中形成一致的定植。类似地用FP 2-A11接种的大鼠直到53 +/- 12.3 dpi才显示出任何迹象,此时所有大鼠都出现后肢轻瘫。仅在脑和骨中存在显著的定植,仅轻微累及肺。因此,这些ENU 1564亚系在其体内肿瘤生长和病变发展的表观速率、其从原位植入部位转移的能力以及在实验转移测定中定殖的组织谱方面不同。这两个克隆提供了可重复的模型,乳腺癌转移在同基因宿主,特别是脑和骨。
An animal model for breast cancer, brain and bone metastasis was developed using ENU1564, a cell line established from a metastatic mammary adenocarcinoma induced by N-ethyt-N-nitrosourea in a female Berlin-Druckrey IV rat. The original tumor isolate (designated FP1) spontaneously metastasizes to regional lymph nodes and lung following orthotopic inoculation into mammary fat pad (mfp) and metastasizes widely following left cardiac ventricle (LV) inoculation. From FP1, two sublines were selected from brain metastases (designated Br7-C5) or from slowly growing colonies in vitro (FP2-A11), then cloned and compared in assays of spontaneous and experimental metastasis. After inoculation of 10(5) cells into mfp, Br7-C5 formed large tumors at the inoculation site (9.4 +/- 3.3 g) and spontaneously metastasized to lung and lymph node by 55 days post-inoculation (dpi). In contrast, FP2-A11 produced much smaller tumors within mfp (0.6 +/- 0.3 g) and failed to metastasize by 55 dpi. Rats inoculated via the LV with 10(4) Br7-C5 cells developed signs of weight loss, head tilt, and dyspnea by 24 +/- 1.4 dpi with consistent colonization of brain, bone, lung, heart, kidney, and stomach. Rats inoculated similarly with FP2-A11 showed no signs until 53 +/- 12.3 dpi, when all developed rear limb paresis. There was significant colonization of only brain and bone, with only minor lung involvement. These ENU1564 sublines thus differ in their apparent rates of tumor growth and lesion development in vivo, their capacity to metastasize from orthotopic implantation sites, and in the spectrum of tissues colonized in experimental metastasis assays. Both clones provide reproducible models of breast cancer metastasis in syngeneic hosts, particularly to brain and bone.