乳腺癌干细胞标志物CD44/CD24与ALDH1的相关性分析
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摘要
目的分析CD44/CD24与乙醛脱氢酶1(ALDH1)两种乳腺癌干细胞标记物表达的阳性细胞比率及其相关性。方法收集培养4例乳腺癌转移胸腔积液和8株乳腺癌细胞系,进行CD44/CD24与ALDH1的标记染色,应用流式细胞术检测CD44~+CD24-与ALDH1~+细胞亚群的比例,并分析两种标记物之间的相关性。结果 8株乳腺癌细胞系CD44~+CD24-细胞亚群比例仅2株高达85%以上,其余均在5%以下; ALDH1~+细胞亚群比例总体较低,在0. 98%-25. 2%之间。4例胸腔积液中,CD44~+CD24~-细胞亚群比例较高,ALDH1~+细胞亚群则比例波动较大。乳腺癌细胞系CD44~+CD24-与ALDH1~+细胞亚群比例的相关性分析显示,两种标记物无相关性(r=-0. 168 3,P=0. 383)。对ALDH1~+、ALDH1~-与未标记细胞中CD44~+CD24~-细胞亚群比例分别进行比较分析,未见差异。结论 CD44/CD24与ALDH1两种乳腺癌标记物在乳腺癌细胞中的表达是独立的,二者没有相关性。
Objective To analyze the positive ratio of breast cancer stem cells marker CD44/CD24 and acetaldehyde dehydrogenase 1( ALDH1) and their correlation. Methods Four cases of breast cancer metastatic pleural effusion and eight breast cancer cell lines were collected and cultured,and then stained with two breast cancer stem cell markers( CD44/CD24 and ALDH1). The ratios of CD44~+CD24-and ALDH1~+subpopulation were detected by flow cytometry,and the correlation between two markers was analyzed.Results The ratios of CD44~+CD24-subpopulation in 2 of 8 breast cancer cell lines were higher than 85%,while the ratios in the rest cell lines were below 5%. The ratio of ALDH1~+subpopulation was relatively low,from 0. 98% to 25. 2%. In 4 cases of pleural effusion,the proportion of CD44~+CD24~- subpopulation was high in total,however,the ratio of ALDH1~+subpopulation fluctuated greatly.And there was no significant correlation between the expression of CD44/CD24 and ALDH1( r =-0. 168 3,P = 0. 383). Furthermore,the ratio of CD44~+CD24-subpopulation in ALDH1~+,ALDH1~- and unlabeled cells showed no difference. Conclusion The expression of CD44/CD24 and ALDH1 in breast cancer cell is independent and there is no correlation between them.
Objective To analyze the positive ratio of breast cancer stem cells marker CD44/CD24 and acetaldehyde dehydrogenase 1( ALDH1) and their correlation. Methods Four cases of breast cancer metastatic pleural effusion and eight breast cancer cell lines were collected and cultured,and then stained with two breast cancer stem cell markers( CD44/CD24 and ALDH1). The ratios of CD44~+CD24-and ALDH1~+subpopulation were detected by flow cytometry,and the correlation between two markers was analyzed.Results The ratios of CD44~+CD24-subpopulation in 2 of 8 breast cancer cell lines were higher than 85%,while the ratios in the rest cell lines were below 5%. The ratio of ALDH1~+subpopulation was relatively low,from 0. 98% to 25. 2%. In 4 cases of pleural effusion,the proportion of CD44~+CD24~- subpopulation was high in total,however,the ratio of ALDH1~+subpopulation fluctuated greatly.And there was no significant correlation between the expression of CD44/CD24 and ALDH1( r =-0. 168 3,P = 0. 383). Furthermore,the ratio of CD44~+CD24-subpopulation in ALDH1~+,ALDH1~- and unlabeled cells showed no difference. Conclusion The expression of CD44/CD24 and ALDH1 in breast cancer cell is independent and there is no correlation between them.
引文
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[15]Biddle A,Liang X,Gammon L,et al.Cancer stem cells in squamous cell carcinoma switch between two distinct phenotypes that are preferentially migratory or proliferative[J].Cancer Res,2011,71(15):5317-5326.
[16]Liu S,Cong Y,Wang D,et al.Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts[J].Stem Cell Reports,2014,2(1):78-91.
[17]Luo M,Brooke M,Wicha MS.Epithelial-mesenchymal plasticity of breast cancer stem cells:implications for metastasis and therapeutic resistance[J].Curr Pharm Des,2015,21(10):1301-1310.
[18]Brooks MD,Burness ML,Wicha MS.Therapeutic implications of cellular heterogeneity and plasticity in breast cancer[J].Cell Stem Cell,2015,17:260-271.
[2]Lytle NK,Barber AG,Reya T.Stem cell fate in cancer growth,progression and therapy resistance[J].Nat Rev Cancer,2018,18(11):669-680.
[3]Ishiguro T,Ohata H,Sato A,et al.Tumor-derived spheroids:Relevance to cancer stem cells and clinical applications[J].Cancer Sci,2017,108(3):283-289.
[4]Qureshi-Baig K,Ullmann P,Haan S,et al.Tumor-initiating cells:a critical review of isolation approaches and new challenges in targeting strategies[J].Mol Cancer,2017,16(1):40.
[5]Al-Hajj M,Wicha MS,Benito-Hernandez A,et al.Prospective identification of tumorigenic breast cancer cells[J].Proc Natl Acad Sci USA,2003,100(7):3983-3988.
[6]DA Cruz Paula A,Lopes C.Implications of different cancer stem cell phenotypes in breast cancer[J].Anticancer Res,2017,37(5):2173-2183.
[7]Saeg F,Anbalagan M.Breast cancer stem cells and the challenges of eradication:a review of novel therapies[J].Stem Cell Investigation,2018,5:39.
[8]Ginestier C,Hur MH,Charafe-Jauffret E,et al.ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome[J].Cell Stem Cell,2007,1(5):555-567.
[9]Huang EH,Hynes MJ,Zhang T,et al.Aldehyde dehydrogenase1 is a marker for normal and malignant human colonic stem cells(SC)and tracks SC overpopulation during colon tumorigenesis[J].Cancer Res,2009,69(8):3382-3389.
[10]Jiang F,Qiu Q,Khanna A,et al.Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer[J].Mol Cancer Res,2009,7(3):330-338.
[11]Visvader JE,Lindeman GJ.Cancer stem cells:current status and evolving complexities[J].Cell Stem Cell,2012,10(6):717-728.
[12]Baccelli I,Trumpp A.The evolving concept of cancer and metastasis stem cells[J].J Cell Biol,2012,198(3):281-293.
[13]Boesch M,Sopper S,Zeimet AG,et al.Heterogeneity of cancer stem cells:rationale for targeting the stem cell niche[J].Biochim Biophys Acta,2016,1866(2):276-289.
[14]Dieter SM,Ball CR,Hoffmann CM,et al.Distinct types of tumorinitiating cells form human colon cancer tumors and metastases[J].Cell Stem Cell,2011,9(4):357-365.
[15]Biddle A,Liang X,Gammon L,et al.Cancer stem cells in squamous cell carcinoma switch between two distinct phenotypes that are preferentially migratory or proliferative[J].Cancer Res,2011,71(15):5317-5326.
[16]Liu S,Cong Y,Wang D,et al.Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts[J].Stem Cell Reports,2014,2(1):78-91.
[17]Luo M,Brooke M,Wicha MS.Epithelial-mesenchymal plasticity of breast cancer stem cells:implications for metastasis and therapeutic resistance[J].Curr Pharm Des,2015,21(10):1301-1310.
[18]Brooks MD,Burness ML,Wicha MS.Therapeutic implications of cellular heterogeneity and plasticity in breast cancer[J].Cell Stem Cell,2015,17:260-271.
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