KAI1/CD82与恶性肿瘤

KAI1/CD82属TM4SF的成员,其结构为细胞膜糖蛋白,有4个高度保守的穿膜结构区.最近的研究表明,KAI1蛋白对多种肿瘤的转移具有抑制作用.有转移潜能的肿瘤细胞或已发生转移的肿瘤组织内KAI1表达下调或不表达.KAI1可作为判断肿瘤预后的一个指标,并将为肿瘤的治疗提供一个新的途径.     

KAI1/CD82的表达与大肠腺癌的相关性分析

目的　初探KAI1/CD82在大肠腺癌组织中的表达。方法　采用免疫组织化学方法 (S -P法 ) ,对 2 41例大肠腺癌组织中KAI1/CD82的表达水平进行半定量研究 ,并探讨其与 2 41例大肠腺癌病理学分级及转移、浸润的相关性。结果　大肠腺癌组织中KAI1/CD82的表达与病理学分级、浸润深度、淋巴结及血道转移呈负相关 (P <0 0 1)。结论　大肠腺癌组织中KAI1/CD82的表达可作为评估肿瘤细胞的转移潜能的一个指标。     

KAI1/CD82和E-cadherin在子宫内膜癌的表达

[目的]研究KAI1/CD82与E-cadherin在子宫内膜癌组织中的表达及其与临床病理参数的关系。[方法]采用免疫组织化学EnVision二步法检测76例子宫内膜癌,15例非典型增生子宫内膜和20例正常增生期子宫内膜组织中KAI1/CD82、E-cadherin的表达。[结果]KAI1/CD82在正常增生期子宫内膜、非典型增生内膜、子宫内膜癌的阳性表达率分别为95%、93.3%和60.5%;E-cadherin在正常增生期子宫内膜、非典型增生内膜、子宫内膜癌的异常表达率分别为0、6.67%和55.26%。KAI1/CD82在子宫内膜癌的表达与组织学分级、肌层浸润程度呈负相关(P=0.000,P=0.01)。E-cadherin在子宫内膜癌的表达与组织学分级及组织学类型有关。KAI1/CD82与E-cadherin在子宫内膜癌中的表达呈显著性相关(P<0.01)。[结论]KAI1/CD82表达下调和E-cadherin异常表达增高与子宫内膜癌的进展有关。     

KAI1/CD82在神经母细胞瘤组织中的表达及其与预后的关系

背景与目的KAI1/CD82是近年来发现的肿瘤转移抑制基因,它的失活与某些肿瘤的进展和浸润有关。本研究旨在通过检测KAI1/CD82蛋白在神经母细胞瘤中的表达,探讨其与神经母细胞瘤临床病理特征和预后的关系。方法用免疫组化EnVision法检测90例神经母细胞瘤瘤组织中KAI1/CD82蛋白的表达,结合临床资料与随访资料进行统计学分析。结果39.3%(11/28)节细胞神经母细胞瘤KAI1/CD82呈阳性表达,14.5%(9/62)神经母细胞瘤KAI1/CD82呈阳性表达(P=0.014)。KAI1/CD82的表达与神经母细胞瘤的分化程度呈显著性正相关,且KAI1/CD82的表达与临床分期呈显著性负相关(P=0.003)。结论KAI1/CD82表达的改变是神经母细胞瘤发生的早期事件,其表达下调是神经母细胞瘤分化和转移的一个潜在标志。此标记物可能作为临床评估预后的综合指标之一。     

KAI1/CD82的表达与乳腺癌转移、预后的关系

目的探讨KAI1/CD82在乳腺癌进展中的作用及其在预后判断中的价值。方法采用免疫组化方法对60例有临床和随访资料的乳腺癌组织进行KAI1/CD82蛋白表达的研究。以15例良性乳腺瘤,15例正常乳腺组织作对照,分析与临床病理指标的关系。结果在乳腺癌原发灶中KAI1/CD82阳性表达41．66%,较正常乳腺组织（80%）、良性乳腺瘤（73．33%）明显减少（P＜0．01、P＜0．05）。KAI1/CD82在有淋巴结转移、周围组织侵润、远处脏器转移肿瘤中表达显著降低（P＜0．01、P＜0．05、P＜0．05）,生存5年以上者的KAI1/CD82蛋白阳性表达率59．38%,明显高于生存时间不超过5年者21．43%（P＜0．01）。患者的术后复发情况与KAI1/CD82表达无关。结论KAI1/CD82的异常表达可能参与了乳腺癌的恶性进展。检测KAI1/CD82的表达对判断肿瘤的侵袭、转移及乳腺癌患者预后有一定的参考价值。     

KAI1/CD82在宫颈鳞癌组织中的表达及其与淋巴结转移的关系

目的:探讨KAI1/CD82蛋白在宫颈鳞癌中的表达及其与宫颈癌淋巴结转移的关系。方法:采用免疫组化S-P法检测KAI1/CD82在10例正常宫颈组织、15例不典型增生宫颈组织及64例宫颈鳞癌组织中的表达,分析表达结果与临床病理特征的关系。结果:从正常宫颈组织到宫颈不典型增生组织再到宫颈癌组织,KAI1/CD82阳性表达率呈递减趋势。KAI1/CD82的表达与宫颈癌病理分级、宫颈癌淋巴结转移明显相关而与临床分期、浸润深度、病理类型、癌灶大小、患者年龄等无关。结论:宫颈鳞癌中KAI1/CD82表达下调与淋巴结转移显著相关,可用来预测淋巴结的转移状况。     

胃腺癌组织中KAI1/CD82蛋白的表达及其意义

目的 探讨KAI1／CD82蛋白在胃腺癌组织中表达及其与胃癌生物学行为的关系。方法应用免疫组织化学技术S-P法检测68例胃腺癌组织中KAI1／CD82蛋白的表达，以20例非肿瘤性胃黏膜组织作对照。对随访14个月～13年的35例做生存分析。结果 68例胃腺癌组织KAI1／CD82蛋白阳性表达率为26、5％（18／68），对照组胃黏膜组织阳性表达率95．0％（19／20）；高／中分化胃腺癌KAI1／CD82蛋白阳性表达率较低分化者为高，分别为41．4％（12／29）、15．4％（6／39），P〈0．05；无淋巴结转移胃腺癌的KAI1／CD82蛋白阳性表达率较有淋巴结转移者为高，分别为45.5％（10／22）、5.3％（8／46），P〈0.05；侵及黏膜及黏膜下层、肌层和浆膜层胃腺癌KAI1／CD82蛋白阳性表达率分别为66、7％（4／6）、34.8％（8／23）、15.4％（6／39），P〈0.05。KAI1／CD82蛋白在Ⅰ～Ⅱ期胃腺癌阳性表达率为37.0％（17／46），在Ⅲ～Ⅳ期胃腺癌中阳性表达率为13.6％（1／22），P〈0.05。KAI1／CD82蛋白阳性患者术后1、3、5、7、10年生存率分别为100.0％（7／7）、85.7％（6／7）、57.1％（4／7）、42.9％（3／7）和28．6％（2／7），而KAI1／CD82阴性患者术后生存率分别为89、3％（25／28）、42、9％（12／28）、14．3％（14／28）、7．1％（2／28）和3、6％（1／28）。KAI1／CD82蛋白阳性患者术后1、3、5、7和10年生存率比KAI1／CD82阴性患者术后1、3、5、7和10年生存率显著提高，P〈0．05。结论 KAI1／CD82蛋白在胃腺癌的表达与肿瘤浸润深度、分化程度、临床分期及淋巴结转移有关，与患者性别、年龄无关。检测KAI1／CD82蛋白有助于临床评估病情，判断预后。     

KAI1/CD82 and MRP1/CD9 Serve as Markers of Infiltration,Metastasis, and Prognosis in Laryngeal Squamous Cell Carcinomas

Objective: The current study explored the expression of KAI1/CD82 and MRP1/CD9 and its significance inlaryngeal squamous cell carcinoma (LSCC). Methods: The expression levels of KAI1/CD82 and MRP1/CD9 in 100LSCC tissue specimens, as well as in 30 para-LSCC non-carcinomatous tissue specimens randomly taken fromthe patients, were assessed using the quantitative polymerase chain reaction (Q-PCR) and immunohistochemistryand correlations with pathological parameters of LSCC and their influence on survival function were analyzed.Results: KAI1/CD82 and MRP1/CD9 showed basically consistent changes in both mRNA and protein expression.Their expression in the 30 LSCC specimens was significantly lower compared with that in the correspondingnon-carcinous tissues (P < 0.01 or 0.05), notably correlating with TNM stage, differentiation degree, clinicalstage, and lymphatic metastasis (P < 0.01 or 0.05), but not gender, age, and LSCC growth sites (P > 0.05). Themedian survival of patients with positive KAI1/CD82 and MRP1/CD9 protein expression was longer than that ofpatients with negative protein expression (P < 0.01 or 0.05). KAI1/CD82 protein expression negatively correlatedwith MRP1/CD9 protein expression in LSCC (χ2= 31.25, P < 0.01). Conclusion: KAI1/CD82 and MRP1/CD9may jointly participate in the development of LSCC. They may serve as the markers for judging the infiltration,metastasis, and prognosis of LSCC.     

KAI1/CD82蛋白表达与食管癌淋巴结转移的关系

目的　探讨KAI1/CD82蛋白表达与食管癌淋巴结转移的关系。方法　应用免疫组化SABC法 ,检测 5 2例食管癌组织中KAI1/CD 82蛋白表达水平。结果　有淋巴结转移食管癌组织和无淋巴结转移食管癌组织中KAI1/CD 82蛋白表达率分别为2 8.6% ( 4 /14 )、73 .7% ( 2 8/3 8) ,两者比较有显著性差异 (P <0 .0 5 )。结论　KAI1/CD 82蛋白表达与食管癌淋巴结转移密切相关     

rAd-p53联合顺铂对胃癌细胞生长及 KAI1／CD82蛋白表达的影响

目的：观察rAd-p53、顺铂（ DDP）单独及联合作用于人胃癌SGC7901细胞后,对肿瘤细胞增殖凋亡情况、KAI1／CD82蛋白表达情况的影响。方法 rAd-p53、DDP单独及联合作用于胃癌SGC7901细胞株24、48、72 h后,CCK-8法测定SGC7901细胞体外增殖活性,流式细胞术检测细胞凋亡率,免疫组化法检测KAI1／CD82蛋白表达情况。结果rAd-p53、DDP单独及联合作用于SGC7901细胞后,细胞增殖被抑制,并呈剂量和时间依赖性,且两药联合组细胞增殖抑制率明显高于单用组,与阴性对照组相比差异均有统计学意义（ P＜0．05）;rAd-p53、DDP单独及两药联合作用SGC7901细胞48h后,细胞凋亡率为36．94％±0．78％、28．79％±2．37％,69．26％±0．63％;rAd-p53、DDP单独及两药联合均可上调KAI1／CD82蛋白表达,且两药联合组更明显。结论 rAd-p53、DDP单独及两药联合均可抑制胃癌SGC7901细胞的生长,诱导其凋亡,二者联合对胃癌细胞的抑制作用增强,rAd-p53可能通过上调KAI1／CD82的表达诱导SGC7901细胞凋亡,同时增强DDP的抗肿瘤作用。     

KAI1/CD82通过Wnt/β-catenin通路对肾癌调控机制的研究

目的:检测KAI1/CD82和p-catenin在肾癌组织及细胞中的表达情况,探讨KAI1/CD82通过Wnt/β-catenin通路对肾癌的调控机制.方法:通过Western blotting检测我院近2年收集的30例肾癌及癌旁组织中CD82及β-catenin的表达;构建KAI1/CD82低表达质粒,转染肾透明细胞癌细胞系786-0和OSRC,划痕实验检测细胞迁移能力;CCK-8法检测细胞增殖能力;Transwell检测细胞侵袭能力;Western blotting检测β-catenin、Axin2、GSK-3β的表达.结果:肾癌组织中CD82表达低于癌旁组织,β-catenin的表达高于癌旁组织.PLTHR-SHKAI1质粒转染786-0和OSRC后,肾癌细胞的迁移、增殖、侵袭能力增强,β-catenin表达增高,Axin2、GSK-3β表达降低.结论:KAI1/CD82和β-catenin在肾癌组织中表达负相关,KAI1抑制肾癌细胞的迁移、增殖、侵袭能力;KAI1/CD82通过Wnt/β-catenin通路相关上游蛋白调控肾癌的发生、发展和转移.     

KAI1 / CD82 和 MMP - 7 在多原发结直肠癌中的表达及临床意义简

目的：探讨KAI1／CD82和MMP-7的表达与多原发结直肠癌浸润、转移的关系。方法：应用免疫组织化学法检测KAI1／CD82和MMP-7在27例多原发结直肠癌及36例单发结直肠癌组织中的表达。结果：多原发结直肠癌组KAI1／CD82阳性表达率为76．7％,单发结直肠癌组KAI1／CD82阳性表达率为50．0％,两组有显著性差异（P〈0．05）。多原发结直肠癌组MMP-7阳性表达率为60．5％,单发结直肠癌组MMP-7阳性表达率为83．3％,两组有显著性差异（P〈0．05）。多原发结直肠癌组和单发结直肠癌组KAI1／CD82、MMP-7的阳性表达率在TNM分期、分化程度、浸润深度和有无淋巴结转移方面差异均有显著性意义。结论：KAI1／CD82、MMP-7的表达与结直肠癌的分期、分化程度、浸润深度和淋巴结转移有关。多原发结直肠癌的浸润、转移与KAI1／CD82和MMP-7的异常表达有关,它们可能协同作用,抑制肿瘤的侵袭和转移能力而促进多原发结直肠癌的发生。     

KAI1/CD82在原发性乳腺癌中的表达及其临床意义

目的:探讨KAI1/CD82在乳腺癌中的表达及其临床意义。方法:采用RT-PCR和免疫组化方法对69例原发性乳腺癌组织、癌旁组织和区域淋巴结组织中KAI1 mRNA和CD82蛋白的表达进行研究。结果:在69例原发性乳腺癌中,癌旁组织中KAI1基因在区域淋巴结转移阴性组和区域淋巴结转移阳性组的mRNA表达无显著性差异(P>0.05)。癌组织和区域淋巴结组织中KAI1基因在区域淋巴结转移阴性组和区域淋巴结转移阳性组的mRNA表达有显著差异(P<0.05)。CD82表达与临床病理类型以及PR表达无相关性(P>0.05),而与临床分期、组织学分级、区域淋巴结转移、远处转移、ER表达有相关性(P<0.05)。结论:KAI1/CD82的表达与乳腺癌的转移及某些临床病理因素有关,具有一定的临床指导意义。     

CD1d-mediated stimulation of natural killer T cells selectively activates hepatic natural killer cells to eliminate experimentally disseminated hepatoma cells in murine liver

Since hepatocellular carcinomas (HCCs) develop from transformed hepatocytes, sometimes in a multicentrical manner, immunological deletion of such small intrahepatic regions should be an important strategy to prevent HCC development. The liver contains abundant innate cell lineages including natural killer (NK) cells and natural killer T (NKT) cells, the latter of which become activated in a CD1d-restricted manner by alpha-galactosylceramide (alpha-GalCer). In our study, we investigated the anti-tumor effect elicited by alpha-GalCer administration against transplanted hepatoma cells in the liver, in comparison with that in extrahepatic sites. alpha-GalCer administration completely suppressed the growth of BNL 1MEA.7R.1 (BNL) hepatoma cells disseminated in the liver of syngeneic BALB/c mouse but had no anti-tumor effect on subcutaneously implanted BNL cells. Hepatic NKT cells became rapidly activated after alpha-GalCer administration compared to splenic NKT cells and then disappeared. Hepatic NK cells substantially increased their population as well as up-regulated their cytotoxic activity against BNL cells, but NK cells in other tissues, including the spleen, blood and lymph node, did not. Anti-asialo GM1 antibody treatment, which depleted NK cells in vivo, resulted in hepatic tumor formation in alpha-GalCer-treated mice, indicating the critical involvement of NK cells in the alpha-GalCer-induced anti-tumor effect in the liver. In conclusion, our study demonstrates clear differences in NK cell activation and anti-tumor effect through stimulation of NKT cells by alpha-GalCer between the liver and extrahepatic tissues. Sequential activation of these innate cell lineages may be an attractive strategy for controlling micro-disseminated hepatoma cells in the liver.     

Parathyroid hormone-related protein (PTHrP) is responsible for production of bone metastasis, but not visceral metastasis, by human small cell lung cancer SBC-5 cells in natural killer cell-depleted SCID mice

We previously established an osteolytic bone metastasis model with multiorgan dissemination in natural killer (NK) cell-depleted severe combined immunodeficient (SCID) mice using human small cell lung cancer cells (SBC-5), which highly express the parathyroid hormone-related protein (PTHrP). In our present study, we evaluated the role of PTHrP on bone metastasis by SBC-5 cells using anti-PTHrP neutralizing antibody (Ab). Anti-PTHrP Ab did not affect the proliferation or cytokine production of SBC-5 cells in vitro. Repeated intravenous injection with anti-PTHrP Ab inhibited the formation of bone metastasis in a dose-dependent manner, while the same treatment had no significant effect on the metastasis to visceral organs (lung, liver, kidney and lymph node). In addition, treatment with anti-PTHrP Ab improved the elevated serum calcium level, associated with inhibition of osteolytic bone metastasis, suggesting that anti-PTHrP Ab inhibited bone metastasis via suppression of bone resorption probably by neutralizing PTHrP. These findings suggest that PTHrP is essential for bone metastasis, but not visceral metastasis, by small cell lung cancer SBC-5 cells.     

大肠癌Kai-1/CD82基因外显子9区域突变的研究

背景与目的:探讨Kai-1/CD82基因外显子9区域的突变在结直肠癌演进与转移中的意义.材料与方法:提取40例结直肠癌患者的肿瘤组织(24例无淋巴结转移,16例有淋巴结转移)DNA和RNA,PCR扩增DNA,测序判断Kai-1/CD82基因中外显子9区域的突变情况;RT-PCR后经测序Kai-1/CD82基因外显子9缺失情况.结果:40例组织标本中18例出现Kai-1/CD82基因突变;在有淋巴结转移的结直肠癌组织中,突变的频率明显高于无淋巴结转移的结直肠癌组织(P＜0.05),在大肠癌中晚期(Dukes C/D期)明显高于早期(Dukes A/B期)(P＜0.05),而Kai-1/CD82基因的突变频率与结直肠癌患者的年龄,性别,组织学类型以及分化程度无关(P＞0.05).结论:Kai-1/CD82基因突变可能与大肠癌演进、转移有关,检测其突变,可以为判断预后、指导临床治疗提供实验依据.     

KAI1和CD44v6蛋白在骨肉瘤组织中的表达及临床意义

Objective: To investigate the expressions of KAI1 and CD44v6 in human osteosarcoma and the relationship between expressions of them and their clinic pathological features and prognosis. Methods: The expressions of KAI1 and CD44v6 in 87 samples with osteosarcema were detected by S-P immunohistochemistry. Results: Expression of KAI1 had correlation with metastasis of osteosarcoma, and was strongly associated with differentiation of tumor cells. The expression of CD44v6 in osteosarcoma had correlation with metastasis. There was no difference between the expression of KAI1 and CD44v6. Cox model analysis showed that the prognostic factors were KAI1 expression, metastasis and Enneking surgical staging system. Conclusion: The abnormal expression of KAI1 and CD44v6 participate metastasis of osteosarcoma, KAI1 expression, metastasis and Enneking surgical staging system can be used to independently predict the prognosis of osteo-sarcoma patients.     

KAI1/CD82 is a novel target of estrogen receptor-mediated gene repression and downregulated in primary human breast cancer

The cell-surface glycoprotein KAI1 suppresses tumor growth and metastasis in various animal models. Downregulation of KAI1 has been implicated in the progression of cancer. However, the mechanisms of KAI1 inactivation are poorly understood. This is the first study that investigates expression and regulation of KAI1 in human breast cancer. KAI1 expression was analyzed on custom-made tissue microarrays comprising 209 well-characterized breast cancers and normal mammary gland tissue. Strong KAI1 immunoreactivity was observed throughout the normal mammary gland epithelium. In breast cancer tissue, KAI1 immunoreactivity was lost in 161/209 (77%) cases. Strikingly, KAI1 was preferentially lost in estrogen receptor (ER)-positive breast cancers (p < 0.001). This was validated by real-time RT-PCR analyses showing a 7.5-fold downregulation of KAI1 mRNA in ER-positive relative to ER-negative tumors (p = 0.028). Notably, this was also corroborated by Affymetrix microarray expression data of an independent cohort of 49 breast cancers. Class comparison analysis identified KAI1 as downregulated in ER-positive tumors. Subsequently, human breast cancer cell lines were employed to test a potential role of ER-activity in the downregulation of KAI1, as suggested by our expression analyses. Exposure of ER-positive breast cancer cells to fulvestrant, a clinically approved ER-antagonist that reverses ER-mediated gene repression, induced a significant upregulation of KAI1 and inhibited cell proliferation as well as migration. In summary, we demonstrate for the first time that KAI1 is a target of ER-mediated gene-repression, and thus, it is downregulated in ER-positive breast cancer. Importantly, KAI1 might be reinducible by endocrine therapy with ER-antagonists in patients suffering from ER-positive breast cancer.