Cancer stem cell populations in lymphoma in dogs and impact of cytotoxic chemotherapy.
Cancer stem cell populations in lymphoma in dogs and impact of cytotoxic chemotherapy.
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DOI：
10.1111/vco.12447
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发表时间：
2019-03
影响因子：
2.1
通讯作者：
Dow S
中科院分区：
文献类型：
--
作者：
Hartley G;Elmslie R;Murphy B;Hopkins L;Guth A;Dow S
化疗后的癌症复发部分归因于癌症干细胞（CSC）的存在，其驱动肿瘤生长和转移，并且对细胞毒性化疗的作用具有高度抗性。因此，细胞毒性化疗选择耐药CSC群体，最终导致肿瘤复发。目前关于CSC在淋巴瘤犬中的作用以及化疗对CSC群体的影响知之甚少。因此，我们使用肿瘤抽吸物和流式细胞术分析一组CSC标志物，前瞻性定量了患有B细胞和T细胞淋巴瘤的犬中的CSC群体。此外，进行体外研究以确定化疗抗性对淋巴瘤细胞的干细胞表型和干细胞特性的影响。我们发现，与正常淋巴结的B细胞相比，患有B细胞淋巴瘤的狗中表达CSC标志物的肿瘤细胞的百分比显著增加。在患有T细胞淋巴瘤的犬中观察到类似的结果。体外研究表明，选择对CHOP化疗耐药的淋巴瘤细胞与化疗敏感的肿瘤细胞相比，CSC标志物的表达显著上调，在培养中更容易形成球状体，并表达显著更高的醛脱氢酶活性。在患有复发性B细胞淋巴瘤的肿瘤样品犬中观察到类似的结果。这些发现表明，细胞毒性化疗可以导致肿瘤细胞与CSC属性，这可能与淋巴瘤复发相对富集。
Cancer relapse following chemotherapy has been attributed in part to the presence of cancer stem cells (CSC), which drive tumor growth and metastasis and are highly resistant to the effects of cytotoxic chemotherapy. As a result, treatment with cytotoxic chemotherapy selects for drug-resistant CSC populations that eventually drive tumor recurrence. Little is known currently regarding the role of CSC in dogs with lymphoma, nor the impact of chemotherapy on CSC populations. Therefore, we prospectively quantitated CSC populations in dogs with B cell and T cell lymphoma, using tumor aspirates and flow cytometric analysis with a panel of CSC markers. In addition, in vitro studies were done to determine the impact of chemotherapy resistance on the stem cell phenotype and stem cell properties of lymphoma cells. We found that the percentages of tumor cells expressing CSC markers were significantly increased in dogs with B cell lymphoma, compared to B cells from normal lymph nodes. Similar findings were observed in dogs with T cell lymphoma. In vitro studies revealed that lymphoma cells selected for resistance to CHOP chemotherapy had significantly upregulated expression of CSC markers, formed spheroids in culture more readily, and expressed significantly greater aldehyde dehydrogenase activity compared to chemotherapy-sensitive tumor cells. Similar results were observed in tumor samples dogs with relapsed B cell lymphoma. These findings suggest that cytotoxic chemotherapy can lead to a relative enrichment of tumor cells with CSC properties, which may be associated with lymphoma recurrence.
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影响因子：
1.8
作者：
Ito D;Frantz AM;Modiano JF
通讯作者：
Modiano JF
影响因子：
11.2
作者：
Chao MP;Alizadeh AA;Tang C;Jan M;Weissman-Tsukamoto R;Zhao F;Park CY;Weissman IL;Majeti R
通讯作者：
Majeti R
DOI：
10.4161/cc.8.20.9761
发表时间：
2009-10-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Ginestier C;Wicinski J;Cervera N;Monville F;Finetti P;Bertucci F;Wicha MS;Birnbaum D;Charafe-Jauffret E
通讯作者：
Charafe-Jauffret E
影响因子：
2.1
作者：
Fowles, J. S.;Dailey, D. D.;Duval, D. L.
通讯作者：
Duval, D. L.
影响因子：
4.7
作者：
Hu, Chen;Li, Hong;Gu, Jianren
通讯作者：
Gu, Jianren