Isolation of stem-like cells from spontaneous feline mammary carcinomas: Phenotypic characterization and tumorigenic potential
Isolation of stem-like cells from spontaneous feline mammary carcinomas: Phenotypic characterization and tumorigenic potential
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DOI：
10.1016/j.yexcr.2012.02.008
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发表时间：
2012-04-15
影响因子：
3.7
通讯作者：
Florio, Tullio
中科院分区：
文献类型：
--
作者：
Barbieri, Federica;Wurth, Roberto;Florio, Tullio
目前的致癌理论指出，只有一小部分肿瘤细胞，即癌症干细胞或肿瘤起始细胞（TIC），负责肿瘤的形成和进展。人乳腺癌起始细胞已被鉴定为表达CD 44的细胞，其保留致瘤活性并显示干细胞样性质。自发性猫科动物乳腺癌（FMC）是一种侵袭性肿瘤，其生物学特性与人类肿瘤相似，我们报道了从FMC中分离的干/祖细胞的分离和表型特征，显示出体外自我更新、持久增殖和体内致瘤性。收集21例FMC样本，进行组织学分类，并通过免疫组织化学方法对Ki 67、EGFR、ER-α和CD 44的表达进行表征。通过在干细胞允许的条件下培养，我们从13个FMCs中分离出一个CD 44阳性亚群，该亚群能够在体外存活并增殖为不同大小和形态的乳腺球。当注射到NOD/SCID小鼠中时，FMC干细胞样细胞引发肿瘤，产生细胞异质性并重现原始组织型。在含血清的培养基中，球状体细胞表现出分化特性，如形态学变化所示，CD 44表达的丧失和致瘤性potential.These数据表明，干限定培养的FMC丰富的TIC和验证使用这些细胞作为一个合适的模型，比较肿瘤学研究乳腺生物学和测试治疗策略，旨在消除TIC。(C)2012 Elsevier Inc. All rights reserved.
Current carcinogenesis theory states that only a small subset of tumor cells, the cancer stem cells or tumor initiating cells (TICs), are responsible for tumor formation and progression. Human breast cancer-initiating cells have been identified as CD44-expressing cells, which retain tumorigenic activity and display stem cell like properties. Spontaneous feline mammary carcinoma (FMC) is an aggressive cancer, which shows biological similarities to the human tumor counterpart.We report the isolation and phenotypic characterization of FMC-derived stem/progenitor cells, showing in vitro self-renewal, long-lasting proliferation and in vivo tumorigenicity. Twenty-one FMC samples were collected, histologically classified and characterized for the expression of Ki67, EGFR, ER-alpha and CD44, by immunohistochemistry. By culture in stem cell permissive conditions, we isolated, from 13 FMCs, a CD44-positive subpopulation able to survive and proliferate in vitro as mammospheres of different sizes and morphologies. When injected in NOD/SCID mice, FMC stem-like cells initiate tumors, generating cell heterogeneity and recapitulating the original histotype. In serum-containing medium, spheroid cells showed differentiation properties as shown by morphological changes, the loss of CD44 expression and tumorigenic potential.These data show that stem-defined culture of FMC enriches for TICs and validate the use of these cells as a suitable model for comparative oncology studies of mammary biology and testing therapeutic strategies aimed at eradicating TICs. (C) 2012 Elsevier Inc. All rights reserved.