Spontaneous fusion with, and transformation of mouse stroma by, malignant human breast cancer epithelium

Spontaneous fusion with, and transformation of mouse stroma by, malignant human breast cancer epithelium
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DOI:
10.1158/0008-5472.can-06-1456
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发表时间:
2006-08-15
期刊:
影响因子:
11.2
通讯作者:
Horwitz, Kathryn B.
Horwitz, Kathryn B.
中科院分区:
医学1区
文献类型:
--
作者:
Jacobsen, Britta M.;Harrell, J. Chuck;Horwitz, Kathryn B.

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从乳腺癌患者的胸腔积液中提取的腺癌细胞被注射到裸鼠的乳腺中,并长成实体瘤。来源于这些肿瘤的细胞系表达α -平滑肌肌动蛋白,但不表达人细胞角蛋白7,表明“活化”基质来源于小鼠。有丝分裂细胞主要表现为小鼠多倍体核型,30%的细胞具有小鼠和人类染色体的混合,其中8%的细胞携带小鼠/人类易位。间期细胞核杂交率为64%。在原发异种移植物中也检测到鼠/人杂交细胞核。因此,实体瘤中的合核是由恶性人上皮与周围正常宿主小鼠间质自发融合形成的。转化的间质来源细胞具有致瘤性,具有恶性肿瘤的组织病理学特征,提示肿瘤进展的新机制。
Adenocarcinoma cells from the pleural effusion of a patient with breast cancer were injected into the mammary glands of nude mice and grown into solid tumors. A cell line derived from these tumors expressed alpha-smooth muscle actin but not human cytokeratin 7, indicating "activated" stroma of mouse origin. Cells in mitosis exhibited mainly polyploid mouse karyotypes, but 30% had mixed mouse and human chromosomes, among which 8% carried mouse/human translocations. Nuclei of interphase cells were 64% hybrid. Hybrid mouse/ human nuclei were also detected in the primary xenograft. Thus, synkaryons formed in the solid tumor by spontaneous fusion between the malignant human epithelium and the surrounding normal host mouse stroma. The transformed stroma-derived cells are tumorigenic with histopathologic features of malignancy, suggesting a new mechanism for tumor progression.