CD44v6及nm23-H1表达与肝细胞癌侵袭转移

目的原位检测肝细胞癌(HCC)中CD44v6 mRNA及nm23-H1 mRNA的表达,了解CD44v6 mRNA及nm23-H1 mRNA的表达与HCC侵袭转移的关系,了解HCC中CD44v6 mRNA表达与nm23-H1 mRNA表达的相关性.方法采用PCR法合成CD44v6 cDNA探针,体外转录法合成nm23-H1 cRNA探针,采用原位杂交法检测HCC 33例 CD44v6 mRNA和nm23-H1 mRNA的表达.结果侵袭转移倾向高危组的10例HCC标本中,CD44v6 mRNA和nm23-H1 mRNA的阳性率分别为80.0%(8/10)和40.0%(4/10);侵袭转移倾向低危组的23例HCC标本中,CD44v6 mRNA和nm23-H1 mRNA的阳性率分别为21.7%(5/23)和91.3%(21/23).CD44v6 mRNA的表达与HCC的侵袭转移倾向具有正相关性(P＜0.01),nm23-H1 mRNA的表达与HCC的侵袭转移倾向具有负相关性(P＜0.01),CD44v6 mRNA及nm23-H1 mRNA的表达具有负相关性(P＜0.01).结论检测CD44v6 mRNA及nm23-H1 mRNA的表达可能成为HCC转移预后判断的指标.     

肝癌组织骨桥蛋白及CD44v6的表达与肝癌肝移植术患者预后的意义研究

目的研究骨桥蛋白(OPN)、CD44v6预测肝细胞癌肝移植患者预后效能,为寻求新的受体选择标准提供理论依据。方法收集2002年8月至2006年7月期间在西安交通大学医学院第一附属医院行经典原位肝移植术,且病理确诊为肝细胞癌的病例共30例。应用组化染色法,检测OPN、CD44v6的表达,进行统计分析。结果 30例肝细胞肝癌组织中OPN和CD44v6表达正相关。肝移植术后肿瘤复发转移与符合米兰标准情况显著负相关(P<0.01),与OPN、CD44v6的表达正相关(P<0.05)。在超出米兰标准的患者中,肿瘤复发与OPN、CD44v6阳性表达的相关性更强(P<0.01)。随访期内OPN或CD44v6染色阳性患者的生存率明显低于阴性患者(P=0.001),双阳性患者的生存率最低。对于超米兰标准的肝移植患者更为显著(P=0.004)。结论 OPN、CD44v6可以作为预测肝细胞癌肝移植患者预后的预测标签,联合检测OPN、CD44v6能够更好地反映超米兰标准的肝移植患者预后,检测OPN、CD44v6可以纳入受体选择标准。     

Expression of proliferating cell nuclear antigen and CD44 variant exon 6 in primary tumors and corresponding lymph node metastases of colorectal carcinoma with Dukes＇＇ stage C or D

AIM: To study changes in characteristics of colorectal carcinoma during the metastatic process and to investigate the correlation between cell proliferation activity and metastatic ability of patients with Dukes′ stage C or D.METHODS: Formalin fixed and paraffin embedded materials of primary tumors and corresponding lymph node metastases resected from 56 patients with Dukes′ stage C or D of colorectal carcinoma were stained immunohistochemically with proliferating cell nuclear antigen (PCNA) and CD44variant exon 6 (CD44v6).RESULTS: Thirty-one of 56 patients (55.4 %) expressed PCNA in the primary sites and 36 of 56 patients (64.3 %)expressed PCNA in the metastatic lymph nodes. A significant relation in PCNA expression was observed between the primary site and the metastatic lymph node (0.010＜P＜0.025).Forty-one of 56 patients (73.2 %) expressed CD44v6 in the primary site and 39 of 56 patients (69.6 %) expressed CD44v6 in the metastatic lymph node. There was also an significant relationship of CD44v6 between the primary site and the metastatic lymph node (0.005＜P＜0.010). No difference was observed between expression of CD44v6 and PCNA in the primary site (0.250＜P＜0.500).CONCLUSION: This study partially demonstrates that tumor cells in metastatic lymph node of colorectal carcinoma still possess cell proliferation activity and metastatic ability of tumor cells in primary site. There may be no association between cell proliferation activity and metastatic ability in colorectal carcinoma.     

CD44v6在胃癌胃镜标本和术后标本中的表达及与胃癌生物学行为的关系

目的:研究CD44v6在胃癌胃镜标本和术后标本中的表达,并分析其与胃癌生物学行为的关系.方法:随机选取辽宁医学院附属第二医院普通外科2004-2009年收治的有详细病例资料的胃癌患者50例,应用免疫组织化学方法检测胃镜标本和术后标本胃组织中CD44v6的表达.结果:CD44v6在胃癌胃镜标本、术后标本和转移淋巴结中的表达率分别为60.00%、64.00%、80.77%.显著高于胃良性病变(P＜0.01);CD44v6在肠型胃癌中的表达率显著高于弥漫型胃癌(75.86% vs 47.62%,P＜0.05).胃癌胃镜和术后标本中CD44v6的表达与胃癌浸润深度,TNM分期和淋巴结转移均有关(P＜0.05).CD44v6在胃癌胃镜标本和术后标本中的总体表达率无显著性差异(P＞0.05);相同临床病理参数,CD44v6在胃癌胃镜标本和术后标本中的表达率无显著性差异(P＞0.05).结论:CD44v6可作为术前预测胃癌的发生、病期进展和转移潜能的辅助生物学指标之一.     

Expression of human chorionic gonadotropin, CD44v6 and CD44v4/5 in esophageal squamous cell carcinoma

AIM: To study the relationship between the expression of human chorionic gonadotropin (HCG), CD44v6, CD44v4/5 and the infiltration, metastasis of esophageal squamous cell carcinoma. METHODS: By labeled streptavidin-biotin technique, the expressions of HCG, CD44v6, and CD44v4/5 in 42 patients with esophageal squamous cell carcinoma were examined. RESULTS: The positive rate of HCG expression in patients with lymph node metastasis was 85.71% (18/21), higher than that (57.14%, 12/21) in those without lymph node metastasis (P<0.05). The positive rate of CD44v6 expression was 71.43% (15/21) in lymph node metastasis group, and 38.09% (8/21) in non-metastasis group; there was a significant difference between the two groups (P<0.05). The positive rate of CD44v4/5 expression was 76.19% (16/21) in lymph node metastasis group, and 42.86% (9/21) in non-metastasis group; there was also a significant difference between them (P<0.05). From grade Ⅰ to grade Ⅲ in differentiation, the positive rate of HCG expression was 84.62% (11/13), 70.59% (12/17) and 58.33% (7/12), respectively; there was no significant difference among them (P<0.05). The positive rate of CD44v6 expression in grades Ⅰ-Ⅲ of cancer tissues was 76.92% (10/13), 52.94% (9/17), and 33.33% (4/12) respectively; there was no significant difference among them. The positive rate of CD44v4/5 expression in grades Ⅰ-Ⅲ of cancer tissues was 69.23% (9/13), 64.71% (11/17), and 41.67% (5/12) respectively; there was no significant difference among the three groups. There was no correlation between the positive rates of HCG and CD44v6, CD44v4/5 expression. Cancer cells in carcinomatous emboli and those infiltrating into vascular wall strongly expressed HCG, CD44v6, and CD44v4/5. CONCLUSION: Expression of HCG, CD44v6, and CD44v4/5 in esophageal squamous cell carcinoma is related to its infiltration and metastasis. HCG, CD44v6, and CD44v4/5 have different effects on the infiltration and metastasis of esophageal squamous cell carcinoma.     

腹腔液中CD44和整合素β1表达与胃癌腹膜转移的关系

目的探讨腹腔液中CD44和整合素β1 mRNA表达与胃癌腹膜转移的关系.方法收集50例胃癌患者的腹腔液标本,用RT-PCR法检测其中CD44和整合素β1 mRNA的表达,同时行腹腔液细胞学(PLC)检查.按病灶浸润深度、浆膜类型、PLC检查结果、腹膜转移情况和TNM分期分组,比较不同组之间CD44和整合素β1 mRNA的表达水平.结果腹腔液CD44 mRNA表达水平与浆膜类型(F=4.59,P＜0.05)、腹膜转移有关(t=2.655,P＜0.05),与PLC检查(t=3.126,P＜0.01)和TNM分期密切相关(t=3.453,P＜0.01);腹膜转移组的整合素β1 mRNA表达明显高于未转移组的水平(t=2.241,P＜0.05).结论腹腔液中CD44和整合素β1 mRNA表达与胃癌腹膜转移相关因素及TNM分期密切相关,检测其水平有助于估计胃癌病程进展和患者预后,对腹膜转移的早期诊断也有一定价值.     

骨桥蛋白及 CD44 v6在肺腺癌侵袭转移中的作用

目的：探讨骨桥蛋白（ OPN）及其受体CD44v6在肺腺癌侵袭转移中的作用。方法应用免疫组化方法检测129例癌旁组织、肺原位腺癌（AIS）、伏壁样生长为主型腺癌（LPA）患者手术切除标本中OPN、CD44v6的表达情况。检测H358细胞（原位癌细胞系）和A549细胞中OPN、CD44v6蛋白及mRNA的表达,Transwell 试验观察OPN、CD44 v6对H358细胞、A549细胞侵袭力的影响。结果 OPN、CD44 v6在LPA组织中的表达阳性率显著高于AIS及癌旁组织,AIS高于癌旁组织,OPN与CD44v6的表达呈显著正相关（ P＜0．05）。 OPN、CD44v6及OPN mR-NA、CD44v6 mRNA在A549细胞中的表达水平高于H358细胞。 Transwell试验提示OPN对A549细胞的趋化作用高于H358细胞。使用OPN抗体阻断OPN对两种细胞的趋化作用,两种细胞穿过数均减少;阻断CD44 v6受体通道后,OPN对两种细胞的趋化作用明显减弱。结论 OPN-CD44 v6复合体对肺腺癌的侵袭能力具有重要作用,OPN有望成为评估肺腺癌进展及预测肿瘤转移潜能的指标。     

Relationship between expression of CD105 and growth factors in malignant tumors of gastrointestinal tract and its significance

AIM: Angiogenesis is an important step in the growth of solid malignant tumors. A number of angiogenic factors have been found such as transforming growth factorβ1 (TGF-β1)and vascular endothelial growth factor (VEGF). However,the roles of TGFβ1 and VEGF in gastrointestinal carcinogenesis are still unclear. This study was to investigate the expressions of TGF-β1 and VEGF in gastrointestinal tract malignant tumors, as well as their association with microvessel density (MVD). At the same time, we also observed the localization of TGF-β1 and its receptor CD105 in gastric malignant tumors.METHODS: The expressions of TGF-β1 and CDL05 were detected in 55 fresh specimens of gastric carcinoma and VEGF and CD105 in 44 fresh specimens of colorectal carcinoma by immunohistochemical staining (S-ABC). TGF-β1 and CD105 in 55 gastric carcinoma tissues on the same slide were detected by using double-stain Tmmunohistochemistry (DS-ABC).RESULTS: Among the 55 cases of gastric carcinoma tissues,30 were positive for TGF-β1 (54.55 %). The MVD of TGF-β1 strong positive group (++～+++ 23.22±5.8) was significantly higher than that of weak positive group (+17.56±7.2) and negative group (- 17.46±3.9) (q=4.5, q=5.3207, respectively,P＜0.01). In the areas of high expression of TGF-β1, MVD and the expression of CD105 were also high. Among the 44 cases of colonic carcinoma tissues, 26 were positive for VEGF (59.1%). The expressions of both VEGF and CD105 (MVD)were related with the depth of invasion (F=5.438, P＜0.05;F=4.168, P=0.05), lymph node metastasis (F=10.311, P＜0.01;F=20.282, P＜0.01) and Dukes stage (F=6.196, P＜0.01;F=10.274, P＜0.01), but not with histological grade (F=0.487,P＞0.05). There was a significant correlation between the expression of VEGF and CD105 (MVD) (r=0.720, P＜0.01).CONCLUSION: Over-expression of TGF-β1 and VEGF acts as stimulating factors of angiogenesis in gastrointestinal tumors.CD105, as a receptor of TGF-β1, can regulate the biological effect of TGF-β1 in tumor angiogenesis. MVD marked by CD105 is more suitable for detecting newborn blood vessels.     

Role of relevant immune-modulators and cytokines in hepatocellular carcinoma and premalignant hepatic lesions

AIM To assess the levels of different immune modulators in patients with hepatocellular carcinoma(HCC),in relation to other hepatic diseases.METHODS Eighty-eight patients were included in the current study and represented patients with HCC(20),liver cirrhosis(28) and chronic hepatitis(CH;25),and normal controls(NC;15).Peripheral blood was isolated for immunophenotyping of active myeloid dendritic cells(m DCs;CD1 c and CD40),mature inactive myeloid cells(CD1 c and HLA),active plasmacytoid cells(p DCs;CD303 and CD40),mature inactive p DCs(CD30 and HLA),active natural killer(NK) cells(CD56 and CD161),active NK cells(CD56 and CD314) and inactive NK cells(CD56 and CD158) was done by flow cytometry.Serum levels of interleukin(IL)-2,IL-10,IL-12,IL-1β,interferon(IFN)-α,IFN-γ and tumor necrosis factor(TNF)-αR2 were assessed by ELISA.RESULTS Active m DCs(CD1 C+/CD40+) and inactive m DCs(CD1 c+/HLA+) were significantly decreased in HCC patients in relation to NC(P 0.001).CD40+ expression on active p DCs was decreased in HCC patients(P 0.001),and its level was not significantly changed among other groups.Inactive p DCs(CD303+/HLA+),inactive NKs(CD56+/CD158+) and active NKs(CD56+/CD161+) were not statistically changed among the four groups studied;however,the latter was increased in CH(P 0.05).NKG2 D was statistically decreased in HCC,CH and cirrhosis(P 0.001),and it was not expressed in 63%(12/20) of HCC patients.There was significant decrease of IL-2,IFN-α and IFN-γ(P 0.001),and a significant increase in IL-10,IL-1β,and TNF-αR2(P 0.01,P 0.001 and P 0.001;respectively) in HCC patients.There was inverted correlation between IL-12 and IL-1β in HCC(r =-0.565,P 0.01),with a strong correlation between p DCs(CD303+/CD40+) and NKs(CD56+/CD161+;r = 0.512,P 0.05) as well as inactive m DCs(CD1 c+/HLA+) and inactive NK cells(CD56+/CD158+;r = 0.945,P 0.001).CONCLUSION NKG2 D,CD40,IL-2 and IL-10 are important modulators in the development and progression of HCC.     

抑癌基因PTEN与胃癌细胞分化及侵袭力的机制研究

采用Boyden小室法测定三种不同分化胃癌细胞(SGC-7901、BGC-823、MGC-803、HGC-27)的体外侵袭力、运动力,RT-PCR检测胃癌细胞的PTEN mRNA表达水平,Western blot法检测胃癌细胞FAK、P-FAK蛋白表达水平.发现随着细胞分化程度的升高,PTEN mRNA表达明显增多,P-FAK蛋白表达明显减少,细胞侵袭力和运动力亦明显减弱(P＜0.01或P＜0.05),FAK蛋白表达无明显变化.认为PTEN mRNA、P-FAK蛋白表达水平在评价胃癌细胞体外运动侵袭力方面具有重要价值;PTEN基因可能通过FAK蛋白途径影响胃癌的侵袭转移.     

Expression and significance of CD44s, CD44v6, and nm23 mRNA in human cancer

AIM: To investigate the relationship between the expression levels of nm23 mRNA, CD44s, and CD44v6,and oncogenesis, development and metastasis of human gastric adenocarcinoma, colorectal adenocarcinoma,intraductal carcinoma of breast, and lung cancer.METHODS: Using tissue microarray by immuhistochemical (IHC) staining and in situ hybri-dization (ISH), we examined the expression levels of nm23mRNA, CD44s, and CD44v6 in 62 specimens of human gastric adenocarcinoma and 62 specimens of colorectal adenocarcinoma; the expression of CD44s and CD44v6in 120 specimens of intraductal carcinoma of breast and 20 specimens of normal breast tissue; the expression of nm23 mRNA in 72 specimens of human lung cancer and 23 specimens of normal tissue adjacent to cancer.RESULTS: The expression of nm23 mRNA in the tissues of gastric and colorectal adenocarcinoma was not significantly different from that in the normal tissues adjacent to cancer (P＞0.05), and was not associated with the invasion of tumor and the pathology grade of adenocarcinoma (P＞0.05). However, the expression of nm23 mRNA was correlated negatively to the lymph node metastasis of gastric and colorectal adenocarcinoma (r = -0.49, P＜0.01; r = -4.93, P＜0.01). The expression of CD44s in the tissues of gastric and colorectal adenocarcinoma was significantly different from that in the normal tissues adjacent to cancer (P＜0.05;P＜0.01). CD44v6 was expressed in the tissues of gastric and colorectal adenocarcinoma only, the expression of CD44v6 was significantly associated with the lymph node metastasis, invasion and pathological grade of the tumor (r = 0.47, P＜0.01; r = 5.04, P＜0.01). CD44sand CD44v6 were expressed in intraductal carcinoma of breast, the expression of CD44s and CD44v6 was significantly associated with lymph node metastases and invasion (P＜0.01). However, neither of them was expressed in the normal breast tissue. In addition, the expression of CD44v6 was closely related to the degree of cell differentiation of intraductal carcinoma of breast (x2= 5.68, P＜0.05). The expressional level of nm23mRNA was closely related to the degree of cell differentiation (P＜0.05) and lymph node metastasis (P＜0.01), but the expression of nm23 gene was not related to sex, age, and type of histological classification (P＞0.05).CONCLUSION: Patients with overexpression of CD44s and CD44v6 and low expression of nm23 mRNA have a higher lymph node metastatic rate and invasion. In addition, overexpression of CD44v6 is closely related to the degree of cell differentiation. Detection of the three genes is able to provide a reliable index to evaluate the invasion and metastasis of tumor cells.     

黏附分子CD44的表达及其糖基化与肝癌转移的相关性

目的 探讨CD44S及其变异体CD44v分子的表达和其糖基化与肝癌细胞侵袭转移的关系. 方法 用免疫组织化学法、量子点、RT-PCR、Western blot、细胞免疫荧光染色、甲基化特异性聚合酶链反应等技术检测转移与非转移性肝癌组织、不同转移潜能人肝癌细胞株中CD44S及其变异体CD44v的定位与表达;并应用多重凝集素印迹法检测这些细胞株中CD44v6的糖基化差异.组间均数比较应用方差分析及t检验,多组间等级资料的比较采用Wilcoxon秩和检验,各组间率的比较采用x2检验.结果 免疫组织化学结果显示,CD44S蛋白定位以细胞质为主; CD44v3、CD44v4/5蛋白定位于细胞膜与细胞质;而CD44v6主要定位于细胞膜.组织芯片结果显示,相对于CD44S及其他CD44v,CD44v6在转移组的表达水平高于非转移组(阳性率为75％与46％),差异具有统计学意义(x2=8.828,P＜0.05);量子点检测(t=2.392,P＜0.05)与血清学检测(t=2.56,P＜0.05)也证实这一结果.Western blot结果显示,CD44v6的表达与肝癌细胞转移潜能呈正相关.此外,在MHCC97L、MHCC97H肝癌细胞中CD44v6基因启动子发生不完全甲基化,而在Hep3B细胞中则发生完全甲基化.而且,相对于Hep3B细胞,MHCC97L及MHCC97H细胞中CD44v6蛋白对朝鲜槐凝集素、黑接骨木凝集素及麦胚凝激素的亲和力较高. 结论 在CD44S及其变异体CD44v中,CD44v6蛋白的高表达与肝癌转移潜能的增强呈正相关;其高表达可能与基因启动子低甲基化有关.此外,CD44v6蛋白唾液酸寡糖链的增加可能与肝癌细胞转移潜能增高有关.     

CD44 V6和VEGF在肝癌组织中的表达及其预后价值的研究

目的探讨CD44 V6和VEGF在肝细胞癌(HCC)中的表达及其在临床预后中的价值。方法对随访的40例原发性肝癌临床病理学资料进行回顾性分析分类,并按照1年内有无复发和转移分组,然后进行常规HE染色及CD44 V6、VEGF的免疫组化染色(S_P法)。结果结果CD44 V6和VEGF主要定位于癌细胞的胞膜,部分胞质同时出现阳性表达;在40例肝癌组织中,CD44 V6和VEGF的阳性表达率分别为75%(30/40)和77.5%(31/40);CD44 V6、VEGF在复发和转移组的表达均高达88.9%(16/18,16/18),明显高于未复发和转移组,和肿瘤侵袭转移的发生有相关性(P<0.05),癌组织中的表达均明显高于癌旁组织,而在肿瘤大小及组织学分级间未见明显差异。结论资料提示肝癌组织中CD44 V6和VEGF过表达分析,有助于肝癌侵袭、转移预测和肝癌预后判断。     

肝细胞癌CD44v6和p16基因蛋白的表达及其意义

目的探讨CD44v6和p16基因蛋白表达与肝细胞癌(HCC)转移和预后的关系。方法应用免疫组织化学方法,检测分析110例HCC组织中CD44v6及p116蛋白表达,结合随访资料分析。结果在HCC中,CD44v6和p16阳性表达率分别为42.7%和34.5%。CD44v6阳性表达的HCC转移率高(P<0.05),分化程度和患者>5年生存率低(P<0.05);p16阳性表达的HCC转移率低(P<0.05),分化程度和患者>5年生存率高(P<0.05)。CD44v6与p16表达呈负相关(r=-0.59,P<0.005)。结论CD44v6和p16表达与HCC转移和患者生存期密切相关,检测CD44v6和p16蛋白的表达可作为判断HCC预后的参考指标。     

肝癌转移相关的骨桥蛋白表达及其糖基化的改变

目的 检测骨桥蛋白(OPN)在不同转移潜能肝癌细胞株及肝癌组织中的蛋白表达水平及其糖基化水平,探讨OPN糖基化改变与肝癌转移的相关性及其意义. 方法 用免疫组织化学和Western blot法检测人肝癌组织(非转移组6例、转移组7例)及不同转移潜能人肝癌细胞株(L02、Hep3B、MHCC97L、MHCC97H、HCCLM3、HCCLM6)中OPN蛋白水平;采用免疫沉淀技术纯化肝癌组织中的OPN蛋白,并采用多重凝集素印迹技术检测转移与非转移肝癌组织中OPN糖基化水平差异.数据统计采用t检验和方差分析.结果 OPN在不同转移潜能肝癌细胞株的表达差异具有统计学意义(F=5.04,P＜0.01).在肝癌组织中,转移组OPN蛋白表达水平明显高于非转移组(t=2.447,P＜0.05),相对吸光度值分别为0.69±0.21和0.45±0.14.免疫沉淀技术成功纯化肝癌组织中的OPN蛋白,后续的凝集素印迹结果显示:与非转移组相比,转移组OPN蛋白对凝集素朝鲜槐、红腰果E型、蔓陀罗、刀豆素A的亲和力较低(P值均＜0.05).结论 OPN蛋白表达水平与肝癌转移潜能增强呈正相关;OPN蛋白的α2,3-唾液酸、平分型GlcNAc、多天线、偏二天线的糖链、高甘露糖型N-糖等糖基化水平改变可能与肝癌转移潜能增高有关.     

淋巴归巢受体P选择素、CD44、α6β1在宫颈癌中表达与淋巴转移关系研究

目的探讨P选择素(P-selectin)、CD44、整合素α6β1对宫颈癌淋巴转移的作用。方法应用免疫组织化学方法对比检测35例宫颈鳞状细胞癌原发灶及其淋巴转移灶中P-selectin、CD44、α6β1的表达。结果与原发灶相比,淋巴转移灶中P-selectin阳性率显著降低(P0.05),CD44阳性率无显著变化(P=1.2305),ICAM-1阳性率则显著增高(P0.01)。原发灶中P-selectin与CD44、P-selectin与ICAM-1表达水平均存在显著正相关性(r=0.8737,P0.01;r=0.7957,P0.01),而CD44与α6β1则呈明显负相关(r=-0.6583,P0.01);淋巴转移灶中P-selectin、CD44、α6β1表达水平之间均不存在相关关系;P-selectin原发灶与淋巴转移中表达水平存在明显正相关(r=0.7534,P0.01),CD44原发灶与淋巴转移中表达水平之间无明显相关,α6β1原发灶与淋巴转移中表达水平之间存在明显负相关(r=-0.5361,P0.01)。原发灶中P-selectin表达与肿瘤分化、淋巴结转移存在正相关(r=0.8420,P0.01和r=0.7689,P0.01);CD44表达与肿瘤侵犯深度、淋巴结转移之间存在正相关(r=0.6782,P0.01;r=0.8634,P0.01);α6β1表达与淋巴结转移存在正相关(r=0.6548,P0.01)。结论P-selectin、CD44、α6β1都与宫颈癌淋巴转移相关,其中P-selectin、CD44在淋巴转移的始动阶段发挥重要作用。     

黏附分子CD44变异剪接体6在甲状腺肿瘤中的表达及其临床意义

目的探讨CD44变异剪接体6(CD     

Osteopontin is overexpressed in human papillary thyroid carcinomas and enhances thyroid carcinoma cell invasiveness

The transmembrane glycoprotein CD44v6 is overexpressed in most papillary thyroid carcinomas (PTC). We previously reported that osteopontin (OPN), a secreted glycoprotein that functions as a ligand for CD44v6, is overexpressed in thyrocytes transformed by the RET/PTC oncogene. OBJECTIVE: In this study we asked whether OPN is overexpressed in human PTC samples, and whether its expression correlates with clinical and histological features of the tumors. Furthermore, we wanted to establish the functional role of the CD44-OPN axis in thyroid tumorigenesis. DESIGN: Thyroid samples from 117 patients who had undergone surgical resection of the thyroid gland for benign or malignant lesions were collected. OPN and CD44 expressions were evaluated by immunohistochemistry with specific monoclonal antibodies. OPN expression was correlated with different PTC histological variants, lymph node metastasis, and PTC size. RESULTS: In this study we show that OPN is overexpressed in human PTCs with respect to normal thyroid tissue, follicular adenomas, and multinodular goiters (P < 0.05). The prevalence and intensity of OPN staining were significantly correlated with the presence of lymph node metastases (P = 0.0091) and tumor size (P = 0.0001). We also show that treatment of human PTC cells with recombinant exogenous OPN stimulated Matrigel invasion and activated the ERK and V-AKT murine thymoma viral oncogene homolog 1/protein kinase B; signaling pathways. Blockage of anti-CD44 antibodies prevented these effects. CONCLUSIONS: Given its prevalence and its correlation with aggressive features of human PTCs, we suggest that OPN might be used as a diagnostic and prognostic marker for these tumors. Furthermore, given the role of the OPN-CD44v6 axis in PTC cells, we suggest that CD44 and/or OPN may be molecular targets for therapeutic intervention in aggressive PTCs.