化疗对三阴性乳腺癌CD44+CD24-/low细胞亚群的影响

目的:观察化疗对三阴性乳腺癌CD44+CD24-/low细胞亚群的影响。方法:用0.2、1、5倍药物血浆峰浓度(peak plasma concentration,PPC)的紫杉醇、多西紫杉醇、氟尿嘧啶、表柔比星、长春瑞滨和吉西他滨分别作用人三阴性乳腺癌MDA-MB-231细胞24、48和72h后,MTT法检测细胞生长情况;FCM法检测1倍PPC的各药物作用48h以及细胞复苏后CD44+CD24-/low细胞含量的变化;另外,FCM法检测10例转移性三阴性乳腺癌患者在化疗前后,外周血中CD44+CD24-/low细胞的含量变化。结果:6种药物均可抑制MDA-MB-231细胞增殖。1倍PPC的各药作用后,CD44+CD24-/low细胞含量未明显升高,以氟尿嘧啶组含量降低最为明显(P<0.05)。转移性三阴性乳腺癌患者在化疗后,外周血中CD44+CD24-/low细胞含量降低(P<0.05)。结论:化疗药物紫杉醇、多西紫杉醇、氟尿嘧啶和表柔比星可降低MDA-MB-231细胞株中CD44+CD24-/low细胞亚群的含量。化疗可使转移性三阴性乳腺癌患者外周血中CD44+CD24-/low细胞含量降低。     

乳腺浸润性微乳头状癌中CD44^＋／CD24^-／low和CD24^＋表型细胞的研究

目的研究乳腺浸润性微乳头状癌（invasive micropapillary carcinoma,IMPC）的干细胞表型,从干细胞和上皮间质转化（epithelial—mesenchymal transition,EMT）角度探讨IMPC高侵袭、高转移恶性生物学行为的原因。方法选取术前未经放化疗治疗患者的IMPC82例和乳腺非特殊型浸润性导管癌（invasive ductal carcinoma not otherwise specified,IDC—NOS）80例石蜡包埋组织标本切片,通过免疫组织化学双染技术检测两组肿瘤组织中CD44^＋／CD24^-/low（CD24^-）和CD24^＋的表达、定位和分布情况,并分析其与各临床病理学特征之间的关系。定量资料采用Student’s t检验,定性资料采用Mann-Whitney U检验、Kruskal—Waliis检验、x^2检验或校正x^2检验。两组之间相关性采用Spearman＇s秩相关分析。结果（1）IMPC组肿瘤细胞的CD44^＋／CD24^-/low阳性表达率（48．8％,40／82例）,明显高于IDC—NOS组（31．3％,25／80例）（x^2=5．180,P=0．023）。（2）53．7％（44／82例）的IMPC微细间质组织内见单个散在的CD44^＋／CD24^-/low肿瘤细胞,且该细胞免疫组织化学染色Vimentin及α—SMA阳性,E—Cadherin阴性。IDC—NOS间质内罕见CD44^＋／CD24^-/low肿瘤细胞。（3）IMPC微乳头结构中CD44^＋／CD24^-/low与间质内的CD44^＋／CD24^-/low阳性表达细胞呈明显正相关（r=0．516,P〈0．001）,并且IMPC微乳头结构及间质中CD44^＋／CD24^-/low阳性表达在有无淋巴管侵犯和有无淋巴结外软组织浸润方面的差异均有统计学意义（P〈0．050）,即有淋巴管侵犯及淋巴结外软组织浸润者CD44^＋／CD24^-/low阳性表达率较高。（4）IMPC组中CD24^＋细胞阳性表达率79．3％（65／82例）,明显高于IDC-NOS组（60．0％,48／80例）（x^2=7．126,P=0．008）,且IMPC中淋巴结转移阳性组CD24的表达高于阴性组,差异有统计学意义（x^2=8．834,P=0．003）。结论IMPC肿瘤细胞中干细胞     

Tissue-specific promoters active in CD44+CD24-/low breast cancer cells

It has been proposed that human tumors contain stem cells that have a central role in tumor initiation and posttreatment relapse. Putative breast cancer stem cells may reside in the CD44(+)CD24(-/low) population. Oncolytic adenoviruses are attractive for killing of these cells because they enter through infection and are therefore not susceptible to active and passive mechanisms that render stem cells resistant to many drugs. Although adenoviruses have been quite safe in cancer trials, preclinical work suggests that toxicity may eventually be possible with more active agents. Therefore, restriction of virus replication to target tissues with tissues-specific promoters is appealing for improving safety and can be achieved without loss of efficacy. We extracted CD44(+)CD24(-/low) cells from pleural effusions of breast cancer patients and found that modification of adenovirus type 5 tropism with the serotype 3 knob increased gene delivery to CD44(+)CD24(-/low) cells. alpha-Lactalbumin, cyclo-oxygenase 2, telomerase, and multidrug resistance protein promoters were studied for activity in CD44(+)CD24(-/low) cells, and a panel of oncolytic viruses was subsequently constructed. Each virus featured 5/3 chimerism of the fiber and a promoter controlling expression of E1A, which was also deleted in the Rb binding domain for additional tumor selectivity. Cell killing assays identified Ad5/3-cox2L-d24 and Ad5/3-mdr-d24 as the most active agents, and these viruses were able to completely eradicate CD44(+)CD24(-/low) cells in vitro. In vivo, these viruses had significant antitumor activity in CD44(+)CD24(-/low)-derived tumors. These findings may have relevance for elimination of cancer stem cells in humans.     

Clinical implications of CD44+/CD24- tumor cell ratio in breast cancer

PURPOSE: To investigate the association of the CD44+/CD24- cancer stem cell (CSC) ratio with clinicopathologic features and its prognostic value in breast cancer. Materials and Methods: The CD44+/CD24- CSC ratio was determined in formalin-fixed, paraffin-embedded breast cancer tissues from 1350 breast cancer patients by double immunofluorescence staining. The Cox regression analysis was performed to evaluate whether the CD44+/CD24- CSC ratio is an independent prognostic factor. The Kaplan-Meier survival analysis was conducted to determine the association of the CD44+/CD24- CSC ratio with cancer-specific survival. Results: The mean average CSC ratio in clinical specimens was 8.06% (range from 1.02% to 37.54%). The CD44+/CD24- CSC ratio, together with histological grade, molecular type, and clinical stage, was independent prognostic factors of breast cancer. The CD44+/CD24- CSC ratio was significantly correlated with estrogen receptor (ER), progesterone receptor (PR), and Ki67, but not the Her-2 and P53 status. Furthermore, the CD44+/CD24- CSC ratio was significantly associated with 5-year breast cancer-specific survival in 1242 cases (88.97% vs. 75.76% vs.52.11% for ≤ 5%, 5%-10% and >10% CSC ratio cases, respectively, p=0.001). The linear regression analysis showed that the CSC ratio was borderlinely correlated with the N stage related (R=0.397 p=0.06), and significantly correlated with distant recurrence (R=0.487, p=0.01) in 1350 specimens. After the survival analysis, the 5-year distant recurrence rates were (57/435 [13.10%] vs. 159/594 [26.77%] vs. 114/213 [53.52%] for ≤ 5%, 5%-10%, and >10% CSC ratio cases, p=0.001). Conclusion: The CSC ratio was an independent prognostic factor for breast cancer as well as a potential predictive marker for chemotherapy in breast cancer.     

CD44+CD24-/low乳腺癌干细胞分选鉴定及其多药耐药性研究

目的:观察MACS免疫磁珠法分选CD44+CD24-/low乳腺癌干细胞活性,并检测其与多药耐药的关系。方法:运用MACS免疫磁珠法从多药耐药乳腺癌细胞株MCF-7/ADR中分选CD44+CD24-/low乳腺癌干细胞,流式细胞术测定分选前后CD44+CD24-/low细胞比例,微球体培养法检测分选细胞自我更新能力,流式检测CD44+CD24-/low细胞表面P-糖蛋白(P-gp)表达水平,Real-time PCR检测多药耐药相关基因MDR1表达水平。结果:MACS免疫磁珠法分选后,CD44+CD24-/low细胞比例为93.85%,其成球能力明显强于non-CD44+CD24-/low细胞亚群。MCF-7/ADR细胞株和CD44+CD24-/low乳腺癌干细胞P-gp表达强度分别为101 177.10±2 171.86和114 906.70±2 560.19,P<0.05。CD44+CD24-/low乳腺癌干细胞MDR1基因表达水平为MCF-7/ADR细胞株的(1.07±0.02)倍,P<0.05。结论:经MACS免疫磁珠法分选所得CD44+CD24-/low细胞亚群有更强的自我更新能力,高表达P-gp蛋白和MDR1基因可能是引起乳腺癌多药耐药的重要原因。     

Selective regain of egfr gene copies in CD44+/CD24-/low breast cancer cellular model MDA-MB-468

Background

The objective of this retrospective study is to investigate laryngeal preservation and long-term treatment results in hypopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) combined with chemotherapy.

Methods

Twenty-seven patients with hypopharyngeal carcinoma (stage II-IV) were enrolled and underwent concurrent chemoradiotherapy. The chemotherapy regimens were monthly cisplatin and 5-fluorouracil for six patients and weekly cisplatin for 19 patients. All patients were treated with IMRT with simultaneous integrated boost technique. Acute and late toxicities were recorded based on CTCAE 3.0 (Common Terminology Criteria for Adverse Events).

Results

The median follow-up time for survivors was 53.0 months (range 36-82 months). The initial complete response rate was 85.2%, with a laryngeal preservation rate of 63.0%. The 5-year functional laryngeal, local-regional control, disease-free and overall survival rates were 59.7%, 63.3%, 51.0% and 34.8%, respectively. The most common greater than or equal to grade 3 acute and late effects were dysphagia (63.0%, 17 of 27 patients) and laryngeal stricture (18.5%, 5 of 27 patients), respectively. Patients belonging to the high risk group showed significantly higher risk of tracheostomy compared to the low risk group (p = 0.014).

Conclusions

After long-term follow-up, our results confirmed that patients with hypopharyngeal carcinoma treated with IMRT concurrent with platinum-based chemotherapy attain high functional laryngeal and local-regional control survival rates. However, the late effect of laryngeal stricture remains a problem, particularly for high risk group patients.     

CD44+/CD24-细胞在乳腺癌组织中比例与乳腺癌远处转移关系

目的:旨在探讨CD44+/CD 24-细胞在乳腺癌组织中的比例与乳腺癌远处转移之间关系。方法:随机选取2003年1 月至2004年10月于天津医科大学肿瘤医院确诊的乳腺癌患者60例,并将其分为30例转移组及30例非转移组（对照组）。 免疫组织化学双重染色技术检测60例患者石蜡切片中CD44+/CD 24-细胞在乳腺癌组织中所占比例,分析其与远处转移之间关系。结果:转移组与对照组中CD44+/CD 24-细胞在乳腺癌组织中所占比例具有显著性差异（χ2= 11.334 ,P < 0.05）。 骨转移中CD44+/CD24-细胞在乳腺癌组织中比例有显著性差异（χ2= 9.250 ,P = 0.01）。 CD44+/CD 24-细胞在乳腺癌组织中5 年无瘤生存期比例有显著性差异（χ2= 8.058,P = 0.005）。结论:CD44+/CD 24-细胞在乳腺癌组织中所占比例与乳腺癌远处转移密切相关,特别是骨转移。      

Brca1 breast tumors contain distinct CD44+/CD24- and CD133+ cells with cancer stem cell characteristics

Introduction

Whether cancer stem cells occur in BRCA1-associated breast cancer and contribute to therapeutic response is not known.

Methods

We generated and characterized 16 cell lines from five distinct Brca1deficient mouse mammary tumors with respect to their cancer stem cell characteristics.

Results

All cell lines derived from one tumor included increased numbers of CD44⁺/CD24^- cells, which were previously identified as human breast cancer stem cells. All cell lines derived from another mammary tumor exhibited low levels of CD44⁺/CD24^- cells, but they harbored 2% to 5.9% CD133⁺ cells, which were previously associated with cancer stem cells in other human and murine tumors. When plated in the absence of attachment without presorting, only those cell lines that were enriched in either stem cell marker formed spheroids, which were further enriched in cells expressing the respective cancer stem cell marker. In contrast, cells sorted for CD44⁺/CD24^- or CD133⁺ markers lost their stem cell phenotype when cultured in monolayers. As few as 50 to 100 CD44⁺/CD24^- or CD133⁺ sorted cells rapidly formed tumors in nonobese diabetic/severe combined immunodeficient mice, whereas 50-fold to 100-fold higher numbers of parental or stem cell depleted cells were required to form few, slow-growing tumors. Expression of stem cell associated genes, including Oct4, Notch1, Aldh1, Fgfr1, and Sox1, was increased in CD44⁺/CD24^- and CD133⁺ cells. In addition, cells sorted for cancer stem cell markers and spheroid-forming cells were significantly more resistant to DNA-damaging drugs than were parental or stem cell depleted populations, and they were sensitized to the drugs by the heat shock protein-90 inhibitor 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride).

Conclusion

Brca1-deficient mouse mammary tumors harbor heterogeneous cancer stem cell populations, and CD44⁺/CD24^- cells represent a population that correlates with human breast cancer stem cells.     

E-cadherin、N-cadherin与CD44+/CD24-/low表型在乳腺癌中表达的相关性及其意义

背景与目的:上皮细胞-间质转化(epithelial-mesenchymal transition,EMT)可以诱导上皮细胞来源的肿瘤表达CD44+/CD24-/low表型细胞,上皮性钙黏蛋白(E-cadherin)和神经性钙黏蛋白(N-Cadherin)是分别表达于上皮细胞和间质细胞的两个重要钙黏蛋白,癌细胞从E-cadherin表达向N-cadherin表达转移是EMT的一个重要机制,此钙黏蛋白转移增加了癌细胞的侵袭转移性.本研究旨在探讨CD44+/CD24-/low表型、E-cadherin及N-cadherin在乳腺癌中的表达及其意义.方法:采用免疫组织化学检测15例正常乳腺组织、20例乳腺癌癌旁组织(癌边缘2～5 cm)、58例乳腺癌组织及18例腋窝转移淋巴结组织中CD44+/CD24-low表型、E-cadherin及N-cadherin的表达,分析其与乳腺癌发生及浸润转移的关系.结果:正常乳腺组织、乳腺癌癌旁组织、乳腺癌组织和腋窝转移淋巴结组织中CD44+/CD24-/low表型表达率分别为6.7%、10.0%、41.4%和44.4%,E-cadherin阳性表达率分别为100%、90.0%、51.7%和33.3%,N-cadherin阳性表达率分别为0、15.0%、44.8%和55.6%,3种蛋白在正常乳腺组织、乳腺癌癌旁组织、乳腺癌组织和腋窝转移淋巴结组织中的表达差异均有统计学意义(P＜0.05).CD44+/CD24-/low表型表达与E-cadherin及N-cadherin表达有显著差异,且与E-cadherin表达关联程度较强,与N-cadherin表达关联程度相对较弱.E-cadherin 表达与N-cadherin表达有显著差异,且具有高度相关性(P＜0.05).结论:CD44+/CD24--1/low表型表达增加、E-cadherin蛋白表达降低及N-cadherin蛋白反常表达与乳腺癌的发生及浸润转移有密切的关系;在乳腺癌发展过程中,E-cadherin向N-cadherin转化及CD44+/CD24-/low表型表达增加可能发挥重要作用.     

CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis

Introduction  

A subpopulation (CD44⁺/CD24^-) of breast cancer cells has been reported to have stem/progenitor cell properties. The aim of this study was to investigate whether this subpopulation of cancer cells has the unique ability to invade, home, and proliferate at sites of metastasis.     

Prevalence of CD44+/CD24-/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis.

PURPOSE: Breast cancer is composed of phenotypically diverse populations of cancer cells. The ability to form breast tumors has been shown by in vitro/in vivo studies to be restricted to epithelial tumor cells with CD44(+)/CD24(-/low) characteristics. Validation of these findings with respect to detection in clinical samples, prognosis, and clinical relevance is in demand. EXPERIMENTAL DESIGN: We investigated breast cancer tissues for the prevalence of CD44(+)/CD24(-/low) tumor cells and their prognostic value. The study included paraffin-embedded tissues of 136 patients with and without recurrences. In addition, a breast cancer progression array with normal, carcinoma in situ, and carcinoma tissues was analyzed. We applied double-staining immunohistochemistry for the detection of CD44(+)/CD24(-/low) cells. Evaluation was by microscopic pathologic inspection and automated image analysis. RESULTS: CD44(+)/CD24(-/low) cells ranged from 0% to 40% in normal breast and from 0% to 80% in breast tumor tissues. The prevalence of CD44(+)/CD24(-/low) tumor cells in 122 tumors was < or =10% in the majority (78%) of cases and >10% in the remainder. There was no significant correlation between CD44(+)/CD24(-/low) tumor cell prevalence and tumor progression. Although recurrences of tumors with high percentages of CD44(+)/CD24(-/low) tumor cells were mainly distant, preferably osseous metastasis, there was no correlation with the event-free and overall survival. There was no influence on the response to different treatment modalities. CONCLUSIONS: Our findings suggest that the prevalence of CD44(+)/CD24(-/low) tumor cells in breast cancer may not be associated with clinical outcome and survival but may favor distant metastasis.     

Histological and prognostic importance of CD44+/CD24+/EpCAM+ expression in clinical pancreatic cancer

CD44⁺/CD24⁺/EpCAM⁺ cells have been reported to be cancer stem cells in pancreatic cancer; however, the histological and clinical importance of these cells has not yet been investigated. Here we clarified the characteristics of CD44⁺/CD24⁺/EpCAM⁺ cells in clinical specimens of pancreatic cancer using immunohistochemical assay. We used surgical specimens of pancreatic ductal adenocarcinoma from 101 patients. In view of tumor heterogeneity, we randomly selected 10 high‐power fields per case, and triple‐positive CD44⁺/CD24⁺/EpCAM⁺ expression was identified using our scoring system. The distribution, histological characteristics, and prognostic importance of CD44⁺/CD24⁺/EpCAM⁺ cells were then analyzed. As a result, the distribution of CD44⁺/CD24⁺/EpCAM⁺ cells varied widely among the 101 cases examined, and CD44⁺/CD24⁺/EpCAM⁺ expression was correlated with poor glandular differentiation and high proliferation. Survival analysis showed that CD44⁺/CD24⁺/EpCAM⁺ expression was not correlated with patient outcome; however, CD44⁺/CD24⁺ expression appeared to be correlated with poor prognosis. In conclusion, CD44⁺/CD24⁺/EpCAM⁺ expression overlapped with poorly differentiated cells and possessed high proliferative potential in clinical pancreatic cancer. In particular, the presence of double‐positive CD44⁺/CD24⁺ expression seemed to have clinical relevance, associating with poor prognosis.     

CD44+CD24-/low在基底样乳腺癌中过表达与其恶性预后的相关性研究

目的探讨乳腺癌干细胞样标志物CD44⁺CD24^-/low在基底样乳腺癌(basal-like breast carcinoma, BLBC)中过表达与BLBC恶性预后的相关性。方法 在乳腺癌基因表达分型的基础上, 根据雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体2(Her-2)免疫表型的表达选取乳腺癌组织四组:管腔A组、管腔B/C组、Her-2高表达组及三阴性组;对三阴性组检测CK5/6、EGFR, 分为正常乳腺样型和BLBC型两组;对上述5组进行免疫组化Envision法染色, 选用抗体为CD44、CD24, 观察CD44⁺CD24^-/low表型表达并比较BLBC组与其它各组的差异。结果 (1)三阴性组共60例, CK5/6和或EGFR阳性者41例(68.3%), 确定为BLBC;CK5/6、EGFR阴性者19例(31.7%), 确定为正常乳腺样组;(2)CD44⁺CD24^-/low表型在BLBC组中占78.0%(32/41), 相对于管腔A组37.9%(11/29)、管腔B组25.9%(7/27)、Her-2高表达组17.2%(5/29)、正常乳腺样组26.3%(5/21), 表达增高并具有显著性(P＜0.05);(3)所有150例乳腺癌中(可评价145例)具有CD44⁺CD24^-/low免疫表型者其Ki-67指数增高相对于非CD44⁺CD24^-/low表型具有统计学差异(P＜0.001)。结论 BLBC型乳腺癌表达乳腺癌干细胞样标志物CD44⁺CD24^-/low显著高于其它各型乳腺癌, CD44⁺CD24^-/low与BLBC独特的恶性生物学行为相关。     

CD44+/CD24+表型的宫颈癌Siha细胞对顺铂的耐药及机制研究

背景与目的：肿瘤干细胞的存在是肿瘤细胞抗拒化疗的原因之一。该研究探讨CD44⁺/CD24⁺宫颈癌Siha细胞对顺铂的耐药性及相关机制。方法：体外培养Siha细胞,流式荧光激活细胞分选仪分选CD44⁺/CD24⁺Siha细胞,噻唑蓝(thiazolyl blue,MTT)法检测不同浓度顺铂对细胞的体外抑制情况,采用流式细胞仪检测10 μg/mL顺铂作用于CD44⁺/CD24⁺ Siha细胞24、48和72 h时的细胞凋亡率,实时定量聚合酶链式反应(quantitutive real-time polymerase chain reaction,qRT-PCR)和蛋白［质］印迹法(Western blot)检测CD44⁺/CD24⁺ Siha细胞中Oct-4、ABCG2、Bcl-2的表达,同时设立亲代Siha细胞作为对照。结果：不同浓度顺铂(0.1、1、5、10、15和20 μg/mL)对CD44⁺/CD24⁺ Siha细胞的增殖抑制作用较亲代Siha细胞小［(88.4±1.5)% vs (92.9±1.5)%,(79.9±1.0)% vs (84.7±1.1)%,(69. 8±0.8)% vs (75.1±2.9)%,(59.0±0.7)% vs (65.8±2.7)%,(49.6±0.9)% vs(52.1±0.5)%,(45.1±0.7)% vs (48.8±1.0)%,P<0.05］;与亲代细胞相比,当10 μg/mL顺铂作用于CD44⁺/CD24⁺Siha细胞时,发现在24、48和72 h时的细胞凋亡率均较小［(3.05±0.16)% vs (5.17±0.27)%,(17.94±2.02)%vs (32.60±4.28)%和(40.14±3.01)% vs (56.62±5.32)%,P<0.05］。qRT-PCR和Western blot实验均显示CD44⁺/CD24⁺ Siha细胞高表达Oct-4、ABCG2和Bcl-2,与亲代Siha细胞比较差异有统计学意义(P=0.015)。结论：CD44⁺/CD24⁺ Siha细胞可以抵抗顺铂诱导的细胞凋亡,具有化疗抵抗性,并且高表达肿瘤干细胞表面标志物如Oct-4和ABCG2,该结果在宫颈癌肿瘤干细胞的有效分选以及肿瘤靶向治疗方面有深远意义。     

CD44+/CD24-/low在乳腺癌中的表达及其与含蒽环类药物化疗方案敏感度的关系

目的研究乳腺癌中CD44+/CD24-/low的表达及其与含蒽环类药物化疗方案敏感度的关系。方法 91例乳腺癌接受含蒽环类药物的术前新辅助化疗,2～4个疗程后进行效果评价;采用双染免疫组织化学方法检测化疗前后CD44+/CD24-/low的表达,t检验分析化疗前后CD44+/CD24-/low细胞比例的变化,χ2检验分析乳腺癌CD44+/CD24-/low表型与乳腺癌临床病理参数及化疗疗效的关系。结果乳腺癌中CD44+/CD24-/low阳性表达率为39.6%(36/91),在接受含蒽环类药物的新辅助化疗后乳腺癌中CD44+/CD24-/low细胞比例较化疗前明显增加(P=0.028)。CD44+/CD24-/low阳性组ER阳性率明显低于CD44+/CD24-/low阴性组(25.0%vs.47.3%,P=0.033)。三阴性乳腺癌中CD44+/CD24-/low阳性率明显高于非三阴性乳腺癌(61.9%vs.32.9%,P=0.017)。CD44+/CD24-/low表型与年龄、肿瘤大小、临床分期、病理类型、组织学分级等乳腺癌临床病理参数无明显关系(P>0.05)。CD44+/CD24-/low阳性组的总有效率高于CD44+/CD24-/low阴性组,但两组之间差异无统计学意义(75%vs.69.1%,P=0.542);CD44+/CD24-/low阳性组的病理完全缓解率明显高于CD44+/CD24-/low阴性组(38.9%vs.18.2%,P=0.028)。结论 CD44+/CD24-/low细胞仅存在于部分乳腺癌,CD44+/CD24-/low表型与ER(﹣)、三阴性乳腺癌相关,CD44+/CD24-/low表型与乳腺癌对含蒽环类药物化疗方案的敏感度相关,CD44+/CD24-/low表型可能成为乳腺癌临床化疗疗效的预测指标之一。     

Impact of CD44+CD24- cells on non-sentinel axillary lymph node metastases in sentinel node-positive breast cancer

Although complete axillary lymph node dissection (ALND) is the standard for evaluating axillary status after the identification of a positive sentinel lymph node (SLN) in breast cancer; approximately 40-60% of SLN-positive patients have negative non-SLN. In this study, to explore putative breast cancer stem cells with CD44+CD24- in the SLN, we retrospectively analyzed the expression of CD44+CD24- on metastatic tumor cells within SLNs as a predictive factor for positive non-SLNs (NSLNs). We tested 271 patients for SLNs using serial sectioning with cytokeratin immunohistochemistry (IHC) and hematoxylin-eosin staining and identified 67 patients who had a positive SLN biopsy and complete ALND. CD44 and CD24 expression was detected using double-staining IHC. Twenty-eight (41.8%) out of 67 patients had positive NSLN metastases. Seven positive SLNs with micrometastases were not available for the evaluation of CD24 and CD44 expression. Out of the remaining 60?patients, 19?(31.7%), 44?(73.83%) and 37?(61.7%) patients had CD24+, CD44+ and CD44+CD24- metastatic tumor cells in SLNs, respectively. Positive NSLN metastasis was significantly associated with the primary tumor size (P=0.004), CD24- expression (P=0.04), CD44+ expression (P=0.01) and CD44+CD24- expression (P=0.02). This report provides the first evidence of the existence of a putative stem-like phenotype within the SLN, which is significantly associated with positive NSLN in early breast cancer patients.     

沉默CD44表达对乳腺癌细胞MDA-MB-231增殖与侵袭的影响

目的:探索乳腺癌细胞MDA-MB-231及MCF-7中CD44分子的表达水平差异及沉默CD44对乳腺癌细胞MDA-MB-231增殖、侵袭和迁移的影响。方法:利用qRT-PCR及Western blot技术检测细胞中CD44基因表达水平;设计并合成CD44的siRNA片段(CD44-siRNA)转染乳腺癌细胞,利用qRT-PCR、Western blot技术检测细胞中CD44基因表达水平的变化;MTT检测MDA-MB-231细胞增殖;Transwell侵袭实验检测MDA-MB-231细胞的迁移与侵袭能力变化。结果:CD44在侵袭性乳腺癌细胞MDA-MB-231中的表达高于非侵袭性乳腺癌细胞MCF-7,CD44-siRNA下调了 MDA-MB-231细胞中CD44 mRNA与蛋白水平的表达,并抑制了细胞的增殖和侵袭转移能力。结论:CD44-siRNA能够下调CD44的表达,并有效抑制乳腺癌细胞MDA-MB-231的增殖及其侵袭迁移力。     

CD44分子与乳腺癌

CD44分子属于黏附分子家族中的一员，其CD44的异常表达与乳腺癌的发生、发展和转移密切相关。近年来研究表明乳腺癌干细胞表面高度表达CD44分子，针对CD44分子与乳腺癌干细胞关系的研究，将为乳腺癌的临床治疗提供新的靶点。     

CD44分子与乳腺癌

CD44分子属于黏附分子家族中的一员,其CD44的异常表达与乳腺癌的发生、发展和转移密切相关。近年来研究表明乳腺癌干细胞表面高度表达CD44分子,针对CD44分子与乳腺癌干细胞关系的研究,将为乳腺癌的临床治疗提供新的靶点。