人胃癌组织块裸鼠原位移植/转移模型的建立

 目的　用肿瘤组织块原位移植 ,建立人胃癌裸小鼠原位移植 /转移模型。方法　以人胃低分化腺癌细胞系接种于裸小鼠皮下 ,形成稳定传代的皮下移植瘤 ,再取该肿瘤组织块原位移植于裸鼠胃壁 ,观察移植肿瘤的生长状况、移植成功率和自发转移的发生率。结果　原位移植成功率 (成瘤率 )为 1 0 0 %、局部淋巴结转移率 1 0 0 %、远处淋巴结转移率 90 %、肝转移发生率为 75%。荷瘤鼠的中位生存期为 1 4周 ,晚期出现消瘦和全身衰竭。结论　该裸小鼠原位移植 /转移模型的生物学行为与人胃癌自然生长和转移过程相似 ,可作为一种有价值的工具用于胃癌转移机理和抗转移实验治疗的研究。     

沉默乙酰肝素酶基因对胃癌生物学行为的影响

目的 探讨乙酰肝素酶(HPA)沉默对人胃癌裸鼠移植瘤生长、转移和血管形成的影响.方法 利用人胃癌SGC-7901细胞和HPA被沉默的SGC-7901-HPA-细胞,分别建立6只裸鼠皮下移植瘤模型,观察成瘤的时间、肿瘤生长速度和体积.应用逆转录聚合酶链反应(RT-PCR)和Western blot方法分别检测皮下移植瘤组织中HPA mRNA和蛋白的表达,应用免疫组织化学SP法检测皮下移植瘤组织的微血管密度(MVD).将皮下移植瘤细胞分别注射入6只裸鼠腹腔,建立腹腔转移瘤,并观察成瘤情况.结果 SGC-7901细胞和SGC-7901-HPA-细胞在裸鼠皮下均能生长出移植瘤,分别在接种后第4天后和第7天后出现肉眼可见的肿瘤,接种SGC-7901-HPA-细胞的裸鼠移植瘤生长较慢,MVD为(11.35±1.94)个/高倍视野,明显低于接种SGC-7901细胞组[(20.69±1.20)个/高倍视野,P＜0.05].接种SGC-7901-HPA-细胞与接种SGC-7901细胞的裸鼠皮下移植瘤组织相比,HPA mRNA和蛋白的表达均降低.由SGC-7901细胞皮下移植瘤组织建立腹腔转移瘤的裸鼠,有3只成瘤,在肝脏、大网膜、肠系膜、右肾形成了4处转移灶,且体积较大.而接种SGC-7901-HPA-细胞皮下移植瘤组织的裸鼠,仅有1只在肝脏和右肾形成了转移灶,而且瘤体较小.结论 HPA沉默后抑制了人胃癌在裸鼠体内的生长、转移和血管形成,HPA有可能成为预防和治疗胃癌的一个新靶H点.     

人类胃癌裸鼠淋巴结转移模型的建立

 目的　研究胃癌淋巴结转移动物模型的建立方法。方法　人类胃癌低分化细胞系SGC-7901体外培养、传代并扩增后，收集细胞行皮下种植成瘤，鼠间传代至第6代，以皮下肿瘤组织块原位种植于裸鼠胃壁建立动物模型。种植后第9周处死裸鼠，观察原位种植瘤生长、淋巴结转移及其他脏器转移情况，测定荷瘤裸鼠血清癌胚抗原（CEA）值。结果　原位移植瘤种植成功率100 ％，胃周淋巴结转移率93.3 ％，移植瘤可发生局部浸润及远处脏器转移，荷瘤裸鼠CEA值明显高于正常裸鼠（P＜0.01）。结论　应用SGC-7901细胞系可成功建立胃癌的淋巴结转移动物模型。     

人胃癌裸鼠原位移植瘤模型的建立及其活体荧光成像检测

目的:建立可动态实时监测的人胃癌裸鼠原位移植瘤模型.方法:将稳定表达荧光素酶的人胃癌细胞SGC-7901fLuc+注入裸鼠后肢根部皮下形成皮下移植瘤.待皮下移植瘤瘤块长至直径0.5 cm时,剥取肿瘤组织,应用叠合法将瘤块原位移植于裸鼠胃小弯处,形成原位移植瘤模型.利用小动物活体荧光成像系统,每4日监测移植瘤的进展情况.荷瘤3周后,解剖荧光成像阳性小鼠,利用H-E染色、光镜下观察移植瘤的形态.结果:应用小动物活体荧光成像系统,可在荷瘤裸鼠胃部检测到逐渐增强的荧光信号.荷瘤裸鼠胃部存在肿瘤包块贴附于胃壁,包块直径为0.5 ～1.0 cm,包块周围与相邻组织器官边界清晰,未见粘连,检查腹腔未见转移,未见腹水形成.应用叠合法构建人胃癌裸鼠原位移植瘤模型成功率为95％(19/20).对荷瘤胃组织H-E染色后,可见异常肿瘤细胞,肿瘤包膜完整,符合胃癌组织学特征.结论:成功建立了操作简便、成瘤率高的可动态监测的人胃癌裸鼠原位移植瘤模型,为研究胃癌发生机制、研发抗癌药物提供了理想的实验工具.     

移植性人骨肉瘤OS-732裸鼠模型的建立

目的建立移植性人骨肉瘤裸鼠模型，为骨肉瘤的提供研究实验模型。方法采取皮下细胞悬液注射法与组织块植入接种法，建立人骨肉瘤裸鼠模型。人成骨肉瘤OS-732细胞株体外传代培养后，将l×10^7细胞悬液注入裸鼠腋后皮下（10只裸鼠），或将已成瘤的瘤组织块接种于裸鼠腋后皮下（10只裸鼠），观察肿瘤生长情况。接种后4周处死裸鼠，剥瘤称重，行病理鉴定。比较两种方法的成瘤率、终末瘤体积及瘤重、肿瘤相对增长率；大体观及病理组织学。结果两组裸鼠接种2周后均有局部肿瘤形成，细胞悬液组成瘤率70％，组织块组成瘤率100％，两组成瘤率差异无显著性（P〉0．05）；两组终末瘤体积及瘤重差异具有显著性（均P〈0．05）。细胞悬液组相对增长率高于组织块组，接种后第16天开始两组肿瘤增长率具有显著性差异（P〈0．05）。病理组织学鉴定符合骨肉瘤镜下特点。结论成功建立了移植性人骨肉瘤裸鼠模型，为临床研究提供了可靠方法。     

MIA PaCa-Ⅱ胰腺癌细胞系神经转移动物模型建立的实验研究

目的建立MIA PaCa-Ⅱ人胰腺癌细胞系裸鼠胰腺原位移植瘤模型并观察神经侵袭情况。方法将MIA PaCa-Ⅱ细胞行裸鼠背部皮下接种,建立高转移特性胰腺癌裸鼠皮下移植瘤模型,然后将高转移性移植瘤组织接种于裸鼠胰腺被膜下,分别于4周、6周和8周处死裸鼠行移植瘤组织解剖和病理学检查,测量移植瘤大小和重量,并用HE和银染方法观察神经侵袭情况。结果MIA PaCa-Ⅱ细胞裸鼠皮下接种成瘤率为100.0%（10/10）,皮下移植瘤呈局限性生长,无脏器和神经转移。原位移植4周、6周和8周后,胰腺癌原位移植瘤成瘤率均为100.0%（10/10）,神经转移率分别为50.0%（5/10）、80.0%（8/10）和60.0%（6/10）,并可见多个脏器转移,以肝脏、肝门淋巴结、胃窦转移和腹膜播散多见。结论人胰腺癌细胞系MIA PaCa-Ⅱ裸鼠胰腺原位移植瘤模型为一较理想的＂拟人＂神经浸润转移模型,可用于胰腺癌体内嗜神经性机制的研究。     

脑膜瘤裸鼠移植模型的建立

目的 :探讨建立裸鼠移植脑膜瘤模型的方法 ,为脑膜瘤的基础研究提供实验依据。方法 :将 5例脑膜瘤新鲜切除组织直接接种于 11只裸鼠皮下 ,接种的同时进行脑膜瘤细胞培养观察肿瘤移植物及培养细胞生长情况。结果 :11只接种脑膜瘤新鲜组织的裸鼠有 10只成瘤 ,1例接种物吸收。结论 :脑膜瘤裸鼠皮下接种是建立脑膜瘤动物模型一种比较可靠的方法 ,取材得当是成功的关键之一。     

人卵巢上皮性癌荷瘤裸鼠不良心理应激模型的建立

目的:建立人卵巢上皮性癌荷瘤裸鼠不良心理应激模型,研究不良心理应激对荷瘤裸鼠肿瘤生长的影响.方法:首先采用瘤组织块接种法,建立人卵巢上皮性癌裸鼠皮下移植瘤模型,待肿瘤生长至接种后第12天,将肿瘤大小相近(约8mm)的12只裸鼠随机分为:荷瘤组和荷瘤+应激组,每组6只;荷瘤组自由供食物和水.荷瘤+应激组采用束缚方法给予应激,装置为50mL离心管(打孔3mm,通风良好),操作时依次将应激组小鼠放入离心管中,不挤压动物尾巴,放入管内动物可前后活动.8h后将动物放出,恢复自由供食物和水,每天10:00AM～6:00PM,应激5d/周,共2周;最后观察两组裸鼠生存状态、体重,完成2周应激,结束后第二天,两组裸鼠同时眼眶取血,离心后吸取血清,采用酶联免疫吸附法(ELISA方法)检测两组裸鼠血清中皮质酮、去甲肾上腺素的含量.结果:1)荷瘤+应激组整体生长状态不良,进食及活动不佳,荷瘤+应激组裸鼠体重明显低于荷瘤组,两组比较,差异有显著性(P<0.05).不良心理应激使荷瘤裸鼠体重明显降低;2)荷瘤+应激组血清中皮质酮、去甲肾上腺素的含量明显高于荷瘤组,两组比较,差异有显著性(P<0.05).结论:采用束缚方法成功建立了人卵巢癌荷瘤裸鼠不良心理应激模型,该模型可用于研究不良心理应激对卵巢癌生长的影响.     

人葡萄膜黑色素瘤小鼠肝内种植模型生长行为研究

目的：采用肝内注射人眼葡萄膜恶性黑色素瘤株（MuM2B细胞）方法制备该肿瘤的小鼠肝内种植模型,研究肿瘤在其体内的生物学行为。方法：选用BALB／C-nu裸鼠,将5×10^4个MUM2B细胞注入裸鼠肝脏包膜下。连续观察6周,每周随机处死3只裸鼠以观察成瘤率及侵袭率。采集裸鼠的荷瘤肝脏、心脏、脾脏、肺脏、肾脏、胃和肠等组织器官,常规石蜡切片,HE染色后镜检肿瘤在肝脏内的生长行为及其向其他脏器侵袭和转移的情况。结果：该模型的成瘤率可达83．3％。接种后的前4周,肿瘤在肝脏内浸润性生长,未侵犯周围脏器;接种后第5周,肿瘤开始侵袭肾脏、脾脏、胃和十二指肠的包膜,并可突破胃及肠道的包膜,在其浆膜层中侵袭生长;接种后第6周,肿瘤对肾脏、脾脏、十二指肠和胃的侵袭加剧。肿瘤细胞可侵入裸鼠十二指肠的肌层内生长,亦可侵入裸鼠胃肌层及胃黏膜下层,甚至向胃黏膜肌层内侵袭生长;接种后第6周,肿瘤开始向裸鼠肺脏转移,所有受检裸鼠的肺门组织及肺实质内均可查见转移性瘤灶,转移率达100％;除肺脏外,其余脏器内均未查见转移性瘤灶,提示肺脏是该肝内种植瘤的主要转移靶器官。此外,荷瘤2周后,裸鼠脾脏红髓增生明显,髓内可见大量巨核细胞及髓系来源的粒细胞,呈现白血病样反应;荷瘤4周后,脾脏内星空样现象明显,巨噬细胞活跃,提示裸鼠脾脏组织学改变与荷瘤生长状态密切相关。结论：裸鼠肝内注射MUM2B细胞能够建立起稳定的人葡萄膜黑色素瘤小鼠肝内种植模型。种植的肿瘤细胞在裸鼠肝脏内呈浸润性生长,侵袭包括胃、十二指肠、脾脏及肾脏在内的多个器官,并可远端转移至肺脏。     

左旋棉酚对裸鼠人前列腺癌PC-3细胞皮下移植瘤的生长抑制作用

目的:探讨左旋棉酚对裸鼠人前列腺癌PC-3细胞皮下移植瘤的生长抑制作用及其机制.方法:建立裸鼠人前列腺癌PC-3细胞皮下移植瘤模型,将移植瘤裸鼠80只随机分成4组,每组20只,分别为10.0mg/kg、5.0mg/kg、2.5ng/kg左旋棉酚治疗组和对照组,进行疗效分析与组织病理形态学观察,同时检测肿瘤组织内PCNA、bcl-2、caspase-3和caspase-8的表达.结果:左旋棉酚可使人前列腺癌PC-3细胞荷瘤裸鼠存活率提高,肿瘤体积缩小,肿瘤组织坏死明显,PCNA与bcl-2表达减少,caspase-3和caspase-8表达增加,但高剂量左旋棉酚对PC-3荷瘤裸鼠肝脏和肠道有一定毒性.结论:当治疗剂量大于5.0mg/kg时,左旋棉酚可通过增殖抑制和诱导凋亡,明显抑制裸鼠人前列腺癌PC-3细胞皮下移植瘤的生长.     

人原发性小肠恶性黑色素瘤裸鼠原位移植高转移模型的建立

目的 建立人原发性小肠恶性黑色素瘤裸小鼠原位移植高转移模型.方法 将手术切除的人原发性小肠恶性黑色素瘤原发灶和肝转移灶新鲜瘤组织块分别植入裸鼠小肠黏膜层内,观察原位移植的成瘤率、移植瘤的侵袭性和转移率,并进行形态学、流式细胞分析和染色体核型分析.结果 人小肠恶性黑色素瘤原发灶和肝转移灶新鲜组织均移植成功,建成人原发性小肠(原发灶)恶性黑色素瘤裸鼠原位移植高转移模型(ttSIM-0602)和人原发性小肠(肝转移灶)恶性黑色素瘤裸鼠原位移植肝转移模型(HSIM-0603).HSIM4)602和HSIM-0603模型分别传至21代和23代,共移植裸鼠227只,其肿瘤移植生长率和液氮冻存复苏成活率均为100%.HSIM-0602模型肝转移率为65.7%,肺转移率为84.8%,淋巴结转移率为63.8%.HSIM-0603模型肝转移率为100%,肺转移率为46.7%,淋巴结转移率为71.3%.移植瘤组织病理学为小肠高度恶性黑色素瘤.免疫组织化学显示,S-100蛋白和HMB-45均为阳性表达.电镜下,瘤细胞浆内可见大量的黑色素小体,也可见黑色素复合体.HSIM-0602模型移植瘤细胞DNA指数为1.59±0.07,HSIM-0603模型移植瘤细胞DNA指数为1.71±0.12,均为异倍体.染色体核型分析显示,HSIM-0602模型移植瘤细胞染色体数为55～57条,HSIM-0603模型移植瘤细胞染色体数为57～59条.结论 HSIM-0602和HSIM-0603模型是成功的人原发性小肠恶性黑色素瘤裸鼠原位移植自发性高转移模型,完整地模拟了人原发性小肠恶性黑色素瘤患者的自然临床病理过程,为研究原发性小肠恶性黑色素瘤转移生物学和抗转移治疗提供了理想的动物模型.     

ELAM-1在鼻咽癌裸鼠移植瘤中的表达及其与转移的关系

目的 建立裸鼠鼻咽癌转移模型并探讨 E-选择素（ELAM-1）与鼻咽癌转移的相关性。方法 将鼻咽癌5-8F细胞悬液注射于裸鼠左后肢爪垫，观察裸鼠状态、成瘤情况并测量裸鼠体重及移植瘤长短径；采用连续病理切片苏木精-伊红染色观察移植瘤及转移情况，将16只人鼻咽癌荷瘤裸鼠分为转移组和非转移组；采用免疫组织化学法检测两组移植瘤组织中ELAM-1的表达。 结果 16只裸鼠均成瘤，成瘤率为100.0%，其中10只裸鼠出现转移瘤，转移率为62.5%。建模前，两组裸鼠体重差异无统计学意义［（13.83±0.56）g vs （14.62±0.30） g，t=1.026，P=0.071］。建模后4~7周，裸鼠瘤体体积呈指数增长，且转移组移植瘤增长速度较非转移组快，非转移组裸鼠瘤体体积小于转移组［（198.91 ± 163.29） mm³ vs （268.76 ±174.31） mm³，t=4.376，P=0.005］。ELAM-1在鼻咽癌裸鼠移植瘤、淋巴结转移灶及远处转移灶中的表达均为阳性，主要表达于细胞膜。转移组移植瘤光密度值高于非转移组（0.4497±0.0705 vs 0.0435±0.0082，t=4.388，P＝0.001）。结论 本研究成功构建稳定性好、转移率高的鼻咽癌裸鼠移植瘤转移模型，且ELAM-1在裸鼠移植瘤中高表达，可促进鼻咽癌裸鼠移植瘤生长和转移。     

Development of a metastatic model for human endometrial carcinoma using orthotopic implantation in nude-mice

We have developed an orthotopic model for human endometrial carcinoma in nude mice. The human serous papillary endometrial carcinoma cell line SPEC-2 was injected into the subcutis (ectopic site) or uterine wall (orthotopic site) of athymic mice. Tumors grew in both locations locally. However, only uterine wall tumors produced metastases in regional and distant lymph nodes and to the lungs and liver. Cell lines were established in culture from these uterine tumors and from lung and liver metastases, and then these cells were injected into the uteri of additional mice. The metastatic potential of the lines subsequently established from tumors growing in vivo was not significantly higher than the already highly metastatic parental culture cells. All SPEC-2 cell lines expressed high levels of both 72-kDa and 92-kDa collagenase type IV activity. mRNA for transforming growth factor-alpha, basic fibroblast growth factor, and epidermal growth factor-receptor was constant among the cell lines. These data support the concept that the orthotopic implantation of human endometrial carcinoma cells into the uteri of nude mice provides a valuable model for studying the biology of human endometrial adenocarcinoma.     

肺癌脑转移细胞的筛选及实验动物模型的建立

目的：通过反复裸鼠体内肺癌细胞接种,筛选出特异性脑转移肺癌细胞株,并建立可稳定产生脑转移的肺癌实验动物模型.方法：应用人肺癌细胞株PC-14尾静脉注射接种裸鼠,5周后处死裸鼠,取出脑转移肿瘤组织,行原代培养后再次接种裸鼠,反复几个循环,观察脑转移形成情况.结果：经过4个循环后,筛选出的PC-14/B肺癌细胞尾静脉接种可在裸鼠产生特异脑转移,可应用于建立稳定转移的肺癌脑转移实验动物模型.结论：应用肺癌细胞株行反复裸鼠体内接种,是建立肺癌脑转移实验动物模型的可行方法.     

裸小鼠人宫颈癌组织模型的建立及其生物学特性初探

目的 建立人宫颈癌HeLa细胞在裸小鼠的体表肿瘤模型,并研究其成瘤性及生物学特性。方法 以不同浓度人宫颈癌HeLa细胞悬液在裸小鼠皮下接种建立人宫颈癌裸小鼠模型,观察荷瘤鼠的成瘤率及肿瘤的一般特性,病理检查其组织学特性,流式细胞术检测其生长、凋亡情况,免疫组织化学法检测肿瘤组织中Survivin,Caspase-3和JAK-STAT3蛋白的表达情况。结果 成瘤率为100%,肿瘤生长以局部浸润为主,未见转移瘤,所有新生肿瘤组织符合人宫颈癌细胞组织特点,绝大多数肿瘤细胞处在增殖分化期,标本宫颈癌组织中有Survivin,Caspase-3和STAT3蛋白的阳性表达。结论 成功建立了裸小鼠人宫颈癌组织模型,该模型较好地模拟了人宫颈癌的生物学特性,为进一步研究针对诱导细胞凋亡治疗的新方法提供了理想的动物模型。初步观察了不同浓度HeLa细胞悬液接种生长的肿瘤组织在生长方面的区别。     

人骨肉瘤原位移植模型的建立及生物学特征

目的 用人骨肉瘤细胞系HOS-98建立人骨肉瘤裸鼠胫骨原位移植模型,以探讨宿主器官微环境对人骨肉瘤细胞侵袭及转移等生物学行为的影响。方法 将人骨肉瘤细胞系HOS-98接种于裸鼠皮下,形成移植瘤,用传代移植瘤组织作为移植材料,进行胫骨原位移植及皮下移植。分别于移植后4周和8周处死小鼠,进行病理形态学检查,并对两种方法在成瘤率、生长方式及侵袭、转移等生物学行为比较。结果 两种移植方式在成瘤率及形态学上无明显不同,胫骨原位移植的潜伏期较短,并且生长快于皮下移植方式。皮下移植瘤呈局限性膨胀生长,有不完整的纤维包膜,瘤内类骨基质较少见,未见肺转移,观察8周时无明显消瘦;而胫骨原位移植瘤侵袭周围组织,可见发生肺转移,8周明显消瘦。原位移植的裸鼠血清ALP水平高于皮下移植者。原位移植的X线检查有明显的类似于人的骨性反应。结论 用人骨肿瘤细胞系HOS-98皮下接种的移植瘤作为移植材料是建立肿瘤异位移植的可行途径,裸鼠胫骨微环境较皮下组织更适合于人骨肉瘤的侵袭及转移表达,裸鼠胫骨原位移植模型的恶性生物学行为更接近临床骨肉瘤患者的体内侵袭及转移实际,该原位移植模型为今后的实验研究提供了更加接近患者实际的实验模型。     

The importance of orthotopic implantation to the isolation and biological characterization of a metastatic human clear cell renal-carcinoma in nude-mice

We established a new human renal cell carcinoma system to study some properties of metastatic renal cancer cells and the influence of the organ environment on their metastatic potential. Renal cell carcinoma obtained from a surgical specimen was dissociated enzymatically. Cells were injected into the subcutis, kidney, cecal wall, and spleen of nude mice. Tumors grew in the subcutis and kidney. Only kidney tumors produced distant metastasis. Subcutaneous tumors were avascular and encapsulated, whereas kidney tumors were highly vascularized and invaded the kidney parenchyma. Cell lines were also established from several spontaneous lung metastases. The most metastatic cell line (LM-6) expressed higher levels of basic fibroblast growth factor, gelatinase, and urokinase activity. These results show that human neoplasms are heterogeneous for biologic properties, that orthotopic implantation is essential for the selection, growth, and metastasis of human renal cell carcinoma cells, and that metastatic cells must possess multiple properties to enable them to complete the process.     

Metastasis of human tumors in athymic nude mice

The incidence of metastasis of xenogeneic tumors transplanted to nude mice is controversial. We studied 106 malignant human tumor lines in a total of 1,045 nude mice, and observed metastasis in only 14 instances (1.3%), involving 11 different tumor lines. Three of the lines showed repeated metastasis. Breast tumor lines metastasized with significantly greater frequency than other tumor types. None of the sarcoma lines metastasized. Tumors derived from human metastases were no more prone to metastasizing in nude mice than were tumors derived from primary sites. However, deep penetration of the body wall during growth of the tumor transplant was highly correlated with metastasis (p less than 0.001). Such factors as nude mouse health, tumor size and growth rate, and age and sex of the host mouse were not correlated with metastasis. Serial passage in nude mice did not select for a more malignant tumor line, since the incidence of metastasis did not differ at various passage levels. Thus, metastasis of human malignant tumors in nude mice would appear to depend primarily upon the site of tumor growth in the nude mouse, and upon the intrinsic metastasizing capability of the tumor line employed.     

Neuromedin U is regulated by the metastasis suppressor RhoGDI2 and is a novel promoter of tumor formation, lung metastasis and cancer cachexia

Most deaths from urinary bladder cancer are owing to metastatic disease. A reduction in Rho GDP Dissociation Inhibitor 2 (RhoGDI2) protein has been associated with increased risk of metastasis in patients with locally advanced bladder cancer, whereas in animal models, RhoGDI2 reconstitution in cells without expression results in lung metastasis suppression. Recently, we noted an inverse correlation between tumor RhoGDI2 and Neuromedin U (NMU) expression, suggesting that NMU might be a target of the lung metastasis suppressor effect of RhoGDI2. Here we evaluated whether NMU is regulated by RhoGDI2 and is functionally important in tumor progression. We used small interfering RNA knockdown of endogenous RhoGDI2 in poorly tumorigenic and non-metastatic human bladder cancer T24 cells and observed increased NMU RNA expression. Although NMU overexpression did not increase the monolayer growth of T24 or related T24T poorly metastatic human bladder cancer cells, it did augment anchorage-independent growth for the latter. Overexpression of NMU in T24 and T24T cells significantly promoted tumor formation of both cell lines in nude mice, but did not alter the growth rate of established tumors. Furthermore, NMU-overexpressing xenografts were associated with lower animal body weight than control tumors, indicating a possible role of NMU in cancer cachexia. NMU overexpression in T24T cells significantly enhanced their lung metastatic ability. Bioluminescent in vivo imaging revealed that lung metastases in T24T grew faster than the same tumors in the subcutaneous microenvironment. In conclusion, NMU is a RhoGDI2-regulated gene that appears important for tumorigenicity, lung metastasis and cancer cachexia, and thus a promising therapeutic target in cancer.     

A GFP-labeled Human Colon Cancer Metastasis Model Featuring Surgical Orthotopic Implantation

Colorectal cancer has become a major disease threatening human health. To establish animal models thatexhibit the characteristics of human colorectal cancer will not only help to study the mechanisms underlying thegenesis and development effectively, but also provide ideal carriers for the screening of medicines and examiningtheir therapeutic effects. In this study, we established a stable, colon cancer nude mouse model highly expressinggreen fluorescent protein (GFP) for spontaneous metastasis after surgical orthotopic implantation (SOI). GFPlabeledcolon cancer models for metastasis after SOI were successfully established in all of 15 nude mice and therewere no surgery-related complications or deaths. In week 3, primary tumors expressing GFP were observed inall model animals under fluoroscopy and two metastatic tumors were monitored by fluorescent imaging at thesame time. The tumor volumes progressively increased with time. Seven out of 15 tumor transplanted mice diedand the major causes of death were intestinal obstruction and cachexia resulting from malignant tumor growth.Eight model animals survived at the end of the experiment, 6 of which had metastases (6 cases to mesentericlymph nodes, 4 hepatic, 2 pancreatic and 1 mediastinal lymph node). Our results indicate that our GFP-labeledcolon cancer orthotopic transplantation model is useful with a high success rate; the transplanted tumors exhibitsimilar biological properties to human colorectal cancer, and can be used for real-time, in vivo, non-invasive anddynamic observation and analysis of the growth and metastasis of tumor cells.