黏附分子αvβ3和αvβ5介导肿瘤细胞与肿瘤内皮细胞的黏附

目的 体外分析黏附分子αvβ3和αvβ5及其配体Del-1、L1在肿瘤细胞-内皮细胞黏附中的作用.方法 应用逆转录聚合酶链反应(RT-PCR)和流式细胞分析比较正常肝窦内皮细胞(LSEC)和肝癌的血管内皮细胞T3A上细胞间黏附分子1(ICAM-1)、αvβ3和αvβ5的表达以及缺氧对其表达的调控.分别用RT-PCR和Western blot方法分析6种肿瘤细胞Del-1和L1的表达及缺氧对其表达的调控.使用连续光谱荧光测定仪定量肿瘤细胞在LSEC和T3A上的黏附,并分析抗不同黏附分子的抗体和siRNA对肿瘤细胞一内皮细胞黏附的阻断作用.结果 T3A细胞αvβ3和αvβ5的基础表达高于LSEC,而ICAM-1的基础表达低于LSEC.缺氧上调两种内皮细胞αvβ3和αvβ5的表达,而ICAM-1表达仅在LSEC中升高.在不同肿瘤细胞中,Del-1和L1的基础表达存在明显差异,并且在缺氧条件下受到明显不同的调节.Del-1和L1高表达的肿瘤细胞在T3A细胞的黏附明显高于LSEC,并且在缺氧条件下黏附明显增加,这种黏附可以被抗αvβ3、αvβ5的抗体或沉默β3和β5的小干扰RNA(siRNA)阻断.结论 细胞黏附分子αvβ3、αvβ5及其配体在肿瘤细胞-肿瘤内皮细胞的黏附过程中起重要介导作用.     

人肝癌微血管内皮细胞黏附分子表达特点及其对外周血单个核细胞黏附和跨内皮迁移的影响

目的:研究人肝癌微血管内皮细胞(human liver cancer microvascular endothelial cell,HLCMVEC)上黏附分子表达的特点及其对免疫细胞黏附和迁移的影响.方法:分离培养HLCMVEC,以人肝窦内皮细胞系(liver sinusoid endothelial cell, LSEC)作为正常对照.通过细胞ELISA方法比较多种黏附分子在两种内皮细胞上的表达.外周血单个核细胞(peripheral blood mononuclear cell,PBMC)用荧光染料BCECF标记,将其与HLCMVEC或LSEC共培养,随后采用倒置荧光显微镜和连续光谱荧光仪检测PBMC在两种内皮细胞上的黏附和跨内皮迁移能力;此外,共培养前分别预加各种黏附分子的功能抗体,然后分析各种黏附分子在PBMC与肿瘤微血管内皮细胞黏附和迁移中的作用.结果:HLCMVEC表达CD31、CD34和细胞间黏附分子-3(intercellular adhesion molecule-3,ICAM-3)的水平低于LSEC(P＜0.05),表达ICAM-1和血管细胞黏附分子-1(vascular cell adhesion molecule-l,VCAM-1)的水平明显低于正常LSEC(P＜0.01),但表达整合素αvβ3和αvp5明显高于LSEC(P＜0.01).PBMC在HLCMVEC上的黏附和趋化剂诱导下的跨内皮迁移均显著低于LSEC[黏附:(205.5±46.0) vs (330.5±48.4)个,迁移:(49.0±10.6) vs(110.0±19.2)个,均P＜0.01];该黏附和迁移可被ICAM-1、ICAM-3、VCAM-1抗体明显阻断(P＜0.01),抗CD31抗体对黏附阻断不明显但能阻断跨内皮迁移(P＜0.05).结论:HLCMVEC特有的黏附分子表达特点抑制了PBMC的黏附和跨内皮迁移.     

黏附分子与鼻咽癌的侵袭和转移

黏附分子是一类由细胞产生的膜表面糖蛋白.多项研究已证实,黏附分子可介导肿瘤细胞与细胞外基质、血管内皮细胞、淋巴细胞或其他肿瘤细胞之间的相互作用,因此在恶性肿瘤的侵袭和转移过程中起着重要作用.近年来,已有大量关于黏附分子表达水平的变化可抑制或促进鼻咽癌转移的研究.     

血小板内皮细胞黏附分子-1与肿瘤

血小板内皮细胞黏附分子-1（PECAM-1）是免疫球蛋白超家族中的一种黏附分子,高表达于内皮细胞.近年来研究发现,PECAM-1与肿瘤的发生、血管生成、细胞凋亡以及耐药均相关,可能对肿瘤的诊断与治疗产生重要影响.     

细胞黏附分子与肺癌侵袭转移的关系

细胞黏附分子（CAM）与肿瘤侵袭转移的关系密切,能够介导肿瘤细胞与细胞外基质、血管内皮细胞、实质器官组织细胞以及肿瘤细胞之间的相互作用。现就近年来细胞黏附分子在肺癌侵袭转移中的作用作一综述。     

细胞黏附分子与肺癌侵袭转移的关系

细胞黏附分子(CAM)与肿瘤侵袭转移的关系密切,能够介导肿瘤细胞与细胞外基质、血管内皮细胞、实质器官组织细胞以及肿瘤细胞之间的相互作用。现就近年来细胞黏附分子在肺癌侵袭转移中的作用作一综述。     

整合素ανβ3在肿瘤中的研究进展

整合素是细胞表面重要的黏附分子,介导细胞与胞外基质的相互作用,在肿瘤的发生、侵袭、转移以及肿瘤血管的形成过程中发挥重要的作用.随着对整合素的深入了解,很多整合素分子在肿瘤中的作用也被逐渐地认识,目前采用针对整合素不同分子的克隆抗体、整合素靶向用药及多种方法联合治疗等,通过调节整合素的生物学作用,促进肿瘤细胞凋亡,阻断肿瘤细胞侵袭迁移,抑制肿瘤血管的生成,从而达到治疗肿瘤的目的 .这些研究发现对开拓肿瘤治疗新方案有着重要的意义.     

E-选择素及其配体SLeX介导大肠癌早期黏附的观察

目的:探讨E-选择素及其配体SLeX在大肠癌LoVo细胞与血管内皮细胞ECV304早期黏附中的作用.方法:采用SP法观察E-选择素在内皮细胞ECV304及LoVo中的表达;采用活性染料玫瑰红摄入法检测E-选择素及其配体SLeX在大肠癌LoVo细胞与TNF-α激活内皮细胞ECV304早期黏附中作用.结果:E-选择素和SLeX分别在ECV304和LoVo细胞膜及细胞质内有明确的阳性表达;血管内皮细胞ECV304被TNF-α激活后,其与LoVo细胞间的黏附较激活前明显增加,且具有浓度及时间的依赖性,P＜0.001;用不同浓度的抗E-选择素单抗处理血管内皮细胞ECV304,或用其配体SLeX单抗处理肿瘤LoVo细胞后,随着E-选择素单抗、SLeX单抗浓度增加,细胞相对黏附率逐渐降低(P＜0.001),阻断率逐渐增加(P均＜0.05),提示E-选择素单抗、SLeX单抗可阻断大肠癌细胞与血管内皮细胞间黏附.结论:E-选择素和其配体SLeX是介导血管内皮细胞与大肠癌LoVo细胞系黏附反应的主要早期黏附分子.     

不同亚型的半乳凝素-9对结肠癌LoVo细胞和内皮细胞体外黏附作用的影响

目的 研究不同亚型的半乳凝素-9对结肠癌LoVo细胞侵袭转移相关分子表达的调节作用,以及该调节作用对LoVo细胞与内皮细胞体外黏附作用的影响.方法 半乳凝素-9基因不同亚型的表达载体转染结肠癌LoVo细胞24 h后,分别用逆转录聚合酶链反应(RT-PCR)和Western blot方法检测整合素β1、钙黏着素E、选择素E、细胞间黏附分子-1、CD44和基质金属蛋白酶-9表达的变化.LoVo细胞分别在转染半乳凝素-9、转染半乳凝素-9+半乳凝素-9抗体、转染半乳凝素-9+选择素E抗体和转染半乳凝素-9+β-乳糖条件下进行体外LoVo细胞与内皮细胞的黏附实验.结果 半乳凝素-9L能下调选择素E mRNA和蛋白的表达,半乳凝素-9M和半乳凝素-9S能上调选择素E mRNA和蛋白的表达.体外黏附实验中,转染空载体、转染半乳凝素-9L、转染半乳凝素-9M和转染半乳凝素-9S组的平均荧光强度分别为0.90±0.20、0.94±0.24、1.60±0.11和1.45±0.13.半乳凝素-9M和半乳凝素-9S可促进kVo细胞黏附于内皮细胞(P<0.05),而半乳凝素-9抗体、选择素E抗体和β-乳糖均可抑制此作用.结论 3种不同亚型的半乳凝素-9通过不同的方式调节LoVo细胞选择素E mRNA和蛋白的表达,影响LoVo细胞与内皮细胞的体外黏附;3种不同亚型的半乳凝素-9在介导肿瘤细胞转移过程中的作用可能是不同的.     

CD62P与肿瘤转移的研究新进展

恶性肿瘤的转移和复发是患者预后不良的主要原因,它是一个多环节的复杂过程。其中,肿瘤细胞脱离原发灶进入血循环是一个关键步骤,细胞黏附分子在其中起着重要作用。CD62P是最近发现的黏附分子家族中的一员。它最初是作为血小板活化物被人们认识的,在炎症和栓塞中起中心环节作用。近年来研究表明,CD62P能介导血小板及血管内皮细胞和肿瘤细胞的黏附,促进肿瘤转移。本文就CD62P及其配体的结构和功能特点与肿瘤转移关系的相关研究作一综述。 1 CD62P的分子生物学特征 CD62P又称GMP140、P-选择素或血小板依赖性颗粒表面膜蛋白(PADGEM),由McEver于1989年在激活的血小板膜上发现。其分子量为140kd,基因     

Platelet-tumor cell interaction with the subendothelial extracellular matrix: relationship to cancer metastasis

Dissemination of neoplastic cells within the body involves invasion of blood vessels by tumor cells. This requires adhesion of blood-borne cells to the luminal surface of the vascular endothelium, invasion through the endothelial cell layer and local dissolution of the subendothelial basement membrane. Platelets may participate in each of these steps and thus play a role in the pathogenesis of tumor cell metastasis. To learn more about the possible involvement of platelets we studied the interaction of platelets and tumor cells with cultured vascular endothelial cells and their secreted basement membrane-like extracellular matrix (ECM). Whereas the apical surface of the vascular endothelium lacks adhesive glycoproteins and hence protect the vessel wall against platelet and tumor cell adhesion, the underlying ECM constitute a highly adhesive and thrombogenic surface. Interaction of platelets with this ECM was associated with platelet activation, aggregation and degradation of heparan sulfate in the ECM by means of the platelet heparitinase. The activity of a similar enzyme has been previously correlated with the metastatic potential of various tumor sublines. Biochemical and scanning electron microscopy (SEM) studies have demonstrated that platelets may detect even minor gaps between adjacent endothelial cells and degrade the ECM heparan sulfate. This may expose a larger area of the subendothelium and facilitate subsequent adhesion of blood borne tumor cells. Platelets were also shown to recruit lymphoma cells into minor gaps in the vascular endothelium, that otherwise do not constitute a preferential site of invasion. It is suggested that the platelet heparitinase is involved in the impairment of the integrity of the vessel wall and thus play a role in tumor cell metastasis.     

A new in vitro model for investigation of tumor cell-platelet-endothelial cell interactions and concomitant eicosanoid biosynthesis

We have developed a new in vitro model system to examine tumor cell-platelet-endothelial cell interactions under dynamic conditions. Using the same model, we can determine endogenous eicosanoid metabolism and alterations in the prostacyclin-thromboxane A2 balance associated with interactions among tumor cells, platelets, and endothelial cells. The model consisted of cloned rat aortic endothelial cells grown on gelatin microcarrier beads under dynamic conditions (i.e., spinner culture). Interactions of these endothelial cells with platelets (heparinized rat platelet rich plasma) and/or tumor cells (rat Walker 256 carcinosarcoma) were assessed in an aggregometer. Gelatin beads alone or microcarrier grown endothelial cells did not elicit spontaneous aggregation of platelet rich plasma over a time period of 30 min. Microcarrier grown endothelial cells inhibited tumor cell induced platelet aggregation in a dose dependent fashion (i.e., depending on endothelial cell number). The ability of microcarrier grown endothelial cells to inhibit tumor cell induced platelet aggregation depended on endogenous production of prostacyclin. This conclusion is based on the following results: an increased number of microcarrier grown endothelial cells caused a prolongation of the aggregation lag time; an increased number of microcarrier grown endothelial cells caused a proportionate increase in 6-keto-prostaglandin F1 alpha concentration; an increased number of microcarrier grown endothelial cells was inversely correlated with thromboxane A2 production by platelets; indomethacin pretreatment of microcarrier grown endothelial cells caused a decrease in prostacyclin production and therefore overcame the associated inhibition of tumor cell induced platelet aggregation; and the inhibition of tumor cell induced platelet aggregation in the presence of endogenous prostacyclin produced by microcarrier grown endothelial cells was the same as that observed in the presence of exogenous prostacyclin. Scanning electron microscopy of aggregometry samples revealed: little or no platelet or tumor cell adhesion to gelatin beads alone, a low basal adhesion of tumor cells to microcarrier grown endothelial cells, and large aggregates of platelets and tumor cells located primarily at gaps in the monolayer of indomethacin treated microcarrier grown endothelial cells. This new in vitro model provides a method for examining the effects of eicosanoid metabolism by endothelial cells on tumor cell-platelet-endothelial cell interactions under dynamic conditions.     

Platelet enhancement of tumor cell adhesion to subendothelial matrix: role of platelet cytoskeleton and platelet membrane

Platelet involvement during tumor cell adhesion to subendothelial matrix was examined in vitro. Platelets were subjected to thrombin stimulation and mechanical lysis and examined for their effects on tumor cell adhesion. These treatments altered the platelet ultrastructure and cytoskeletal integrity. Untreated washed rat platelets (WRP) exhibited extensive adhesion to and spreading on substrates and substantially enhanced tumor cell adhesion to the same substrates (i.e., 250% greater than tumor cells without platelets). Thrombin prestimulation of platelets limited platelet adhesion and spreading and platelet facilitation of tumor cell adhesion. Complete mechanical lysis disrupted both the platelet membrane and the cytoskeleton and eliminated the ability of platelets to adhere or to enhance tumor cell adhesion. Partially lysed platelets resembled membrane ghosts and facilitated tumor cell adhesion by a mechanism independent of spreading and cytoskeletal rearrangement. Fractionation studies indicated that platelet cytoskeletal components played a role in the adhesion process. Pretreatment of WRP with cytochalasin A or B dose dependently inhibited microfilament-mediated platelet spreading and platelet-enhanced tumor cell adhesion. Colchicine and vinblastine induced microtubule depolymerization, but they had no observable effect on platelet spreading or platelet-enhanced tumor cell adhesion. It was concluded that platelet-enhanced tumor cell adhesion to subendothelial matrix depends on an intact platelet cytoskeleton and on a platelet membrane component(s) and is mediated by surface contact between platelets and tumor cells. Furthermore, platelet-mediated tumor cell adhesion to subendothelial matrix may involve two mechanisms: one dependent on, and one independent of, platelet spreading and cytoskeletal rearrangement.     

Platelets mediate tumor cell adhesion to the subendothelium under flow conditions: Involvement of platelet GPIIb-IIIa and tumor cell αv integrins

The aim of our study was to explore the role of platelets and their specific integrin receptors in mediating the interaction of 4 human tumor cell lines (3 melanoma and 1 carcinoma) with the extracellular matrix (ECM) under static and arterial flow conditions. Under static conditions, all 4 cell lines adhered to the ECM. The adhesion capacity of all 4 cell lines was virtually abolished by application of flow during incubation with the ECM. Under static conditions, tumor cell adhesion was not affected by adding platelets to the cell suspension and was slightly reduced by pre-coating the ECM with platelets prior to the addition of tumor cells. In contrast, under flow conditions, platelets significantly increased tumor cell adhesion to the ECM, the enhancing effect being more pronounced when platelets were pre-incubated with the ECM prior to the addition of tumor cells than when incubated simultaneously with the cells. Platelet-mediated tumor cell adhesion under flow was markedly inhibited by blockade of the platelet GPIIb-IIIa or of the tumor cell α_v integrins. Platelets of a Glanzmann thrombastenia (GT) patient were unable to support tumor cell adhesion to the ECM under flow. Our results suggest that the interaction of tumor cells with subendothelium-bound platelets under flow conditions is mediated by platelet GPIIb-IIIa and by tumor cell α_v integrins independently of the nature of the β subunit. Int. J. Cancer, 70:201–207, 1997. © 1997 Wiley-Liss, Inc.     

Inhibitory effects of DN-9693 on platelet-enhanced tumor cell attachment to cultured endothelium

The effects of DN-9693, a platelet aggregation inhibitor, on tumor cell attachment to endothelium were investigated to clarify its inhibitory action on metastasis. The role of platelets in the attachment of murine metastasizing tumor cells to endothelium was first examined in vitro. Morphological studies and quantitative isotope measurements revealed that tumor-cell-activated platelets significantly enhanced tumor cell attachment to the endothelium. This amplification is considered to depend on morphological and functional changes of endothelial cells: activated platelets may accelerate endothelial retraction, exposing more reactive subendothelium, and may increase the adhesiveness of endothelial cells. The platelet-enhanced tumor cell attachment to the endothelium was inhibited in the presence of DN-9693. The pretreatment of endothelial cells with the compound was also effective in inhibiting cell attachment. These data suggest that the inhibitory effects of DN-9693 on metastasis are in part mediated by the prevention of tumor cell attachment to the vascular endothelium.     

Endogenous galactoside-binding lectins: a new class of functional tumor cell surface molecules related to metastasis

The formation of secondary tumors by circulating cancer cells (blood-borne metastasis) correlates with an increased tendency of the cells to form emboli by aggregation with other tumor cells or with host cells. Although it is evident that cell-cell recognition and adhesion are mediated by cell surface components, the identity of these molecules is only now being unraveled. Over the last decade an increasing number of studies have demonstrated the presence of endogenous carbohydrate-binding proteins on the surface of various normal cells, and it has been proposed that such lectin-like molecules might be involved in intercellular adhesion.We have shown that various tumor cell lines contain endogenous galactose-specific lectins. Lectin activity was detected at the cell surface by the binding of asialofetuin. This glycoprotein also enhanced the aggregation of the tumor cells. After purification by affinity chromatography on immobilized asialofetuin the lectin activity was associated with two proteins of M_r 14.500 and 34,000. By using polyclonal and monoclonal antilectin antibodies in conjunction with various immunologic techniques we have demonstrated that the endogenous lectins are present on the surface of different tumor cells. Quantitation of cell surface lectins by flow cytometric analyses of antilectin antibody binding revealed that among related tumor cells those exhibiting a higher metastatic potential expressed more lectin on their surface. The binding of monoclonal antilectin antibodies to metastatic cells decreased asialofetuin-induced homotypic aggregation in vitro and suppressed the ability of the cells to form lung metastases after intravenous injection in the tail vein of syngeneic mice. These results strongly implicate the tumor cell surface lectins in cell adhesion and metastasis. We propose that such lectins can increase the ability of tumor cells that enter the blood stream to form aggregates with other tumor cells, or to adhere to host cells or the extracellular matrix and thereby increase their metastatic potential. Other contributing components to tumor cell-host cell interactions are cell surface carbohydrate-binding proteins that have been detected on lymphocytes, platelets, macrophages, hepatocytes, and endothelial cells. These lectin-like molecules might recognize and bind carbohydrates expressed on the surface of tumor cells and enhance emboli formation and organ colonization.     

An in vivo study of the role of the tumor cell cytoskeleton in tumor cell-platelet-endothelial cell interactions

We recently reported that disruption of tumor cell microfilaments or intermediate filaments resulted in an inhibition of the ability of tumor cells to induce the aggregation of homologous platelets in vitro (H. Chopra et al., Cancer Res., 48: 3787-3800, 1988). Previous investigators demonstrated that disruption of the tumor cell cytoskeleton decreases the ability of these cells to form lung colonies. We proposed that this latter effect is due, in part, to decreased interaction of tumor cells with platelets, following their arrest in the microvasculature. To test this hypothesis, B16 amelanotic melanoma cell microtubules, microfilaments, or vimentin intermediate filaments were disrupted with colchicine (50 microns), cytochalasin D (50 microns), or cycloheximide (50 microns), respectively, and then cells were tail vein injected into syngeneic mice. Both cytochalasin D- and cycloheximide-treated cells formed fewer lung colonies than did control cells. Colchicine, however, failed to inhibit lung colony formation. Neither colchicine nor cycloheximide treatment altered initial pulmonary arrest; however, fewer cycloheximide-treated cells remained in the lungs 8 h postinjection. Greater than 90% of control or colchicine-treated cells were found to be associated with activated platelets, and they also demonstrated typical cell membrane process formation 10 min and 8 h post-tumor cell injection. In contrast, less than 10% of cycloheximide-treated cells were in contact with activated platelets 10 min postinjection. However, by 8 h approximately 90% of cycloheximide-treated cells were in contact with activated platelets. This recovery coincided with the reformation of the B16 amelanotic melanoma vimentin intermediate filament network and the reacquisition of the ability to induce platelet aggregation in vitro. Neither colchicine nor cycloheximide treatment altered initial B16 amelanotic melanoma cell adhesion to murine microvessel-derived endothelial cells. This study provides in vivo evidence in support of our previous findings that disruption of certain cytoskeletal elements (i.e., vimentin intermediate filaments) inhibits the tumor cell ability to activate platelets. This study also suggests that platelet activation may stabilize the initial tumor cell arrest in the microvasculature.     

Selectins promote tumor metastasis

Cancer metastasis is facilitated by cell–cell interactions between cancer cells and endothelial cells in distant tissues. In addition, cancer cell interactions with platelets and leukocytes contribute to cancer cell adhesion, extravasation, and the establishment of metastatic lesions. Selectins are carbohydrate-binding molecules that bind to sialylated, fucosylated glycan structures, and are found on endothelial cells, platelets and leukocytes. There are three members of the selectin family: P-selectin expressed on activated platelets and endothelial cells, L-selectin present on leukocytes and E-selectin expressed on activated endothelial cells. Besides the accepted roles of selectins in physiological processes, such as inflammation, immune response and hemostasis, there is accumulating evidence for the potential of selectins to contribute to a number of pathophysiological processes, including cancer metastasis. Cancer cell interactions with selectins are possible due to a frequent presence of carbohydrate determinants—selectin ligands on the cell surface of tumor cells from various type of cancer. The degree of selectin ligand expression by cancer cells is well correlated with metastasis and poor prognosis for cancer patients. Initial adhesion events of cancer cells facilitated by selectins result in activation of integrins, release of chemokines and are possibly associated with the formation of permissive metastatic microenvironment. While E-selectin has been evaluated as one of the initiating adhesion events during metastasis, it is becoming apparent that P-selectin and L-selectin-mediated interactions significantly contribute to this process as well. In this review we discuss the current evidence for selectins as potential facilitators of metastasis.     

The role of adhesion molecules, alpha v beta 3, alpha v beta 5 and their ligands in the tumor cell and endothelial cell adhesion.

Tumor metastasis is a complex process involving the interaction between tumor cells and endothelial cells in which some adhesion molecules play an important role. It was our aim to investigate the role of the adhesion molecules, alpha v beta 3 and alpha v beta 5 and their ligands, developmental endothelial locus-1 (Del-1) and L1, in tumor cell adhesion to endothelial cells in vitro. In this study, the expression and regulation of alpha v beta 3, alpha v beta 5 and intercellular adhesion molecule -1 on liver sinusoidal endothelial cells and liver cancer endothelial cells (T3A) were analyzed by real-time PCR and fluorescent-activated cell sorter. The expression and regulation of the integrin ligands, Del-1 and L1, in six tumor cell lines were analyzed by real-time PCR and western blot. We found the expressions of alpha v beta 3 and alpha v beta 5 were higher on T3A than that on liver sinusoidal endothelial cells, whereas expression of intercellular adhesion molecule-1 was lower on T3A than that on liver sinusoidal endothelial cells. After 24 h hypoxia, the expressions of alpha v beta 3 and alpha v beta 5 were upregulated on T3A and liver sinusoidal endothelial cells; the expression of intercellular adhesion molecule-1 was increased on liver sinusoidal endothelial cells, but remained unchanged on T3A. Del-1 and L1 expression levels were obviously diverse in various tumor cell lines and differentially modulated after 12 h hypoxia. The adhesion of tumor cells with Del-1 and L1 expression was higher in T3A than that in liver sinusoidal endothelial cells, and was significantly increased under hypoxic conditions. Interestingly, the tumor cell adherence could be inhibited by antibodies against alpha v beta 5 and alpha v beta 5, but not by an antibody against intercellular adhesion molecule-1. The adhesion of tumor cells without Del-1 and L1 expression was also higher on T3A than that on liver sinusoidal endothelial cells, but the adhesion could not be inhibited by antibodies against alpha v beta 5, alpha v beta 5 or intercellular adhesion molecule-1, suggesting that other receptors are involved. In conclusion, alpha v beta 5, alpha v beta 5 and their ligands Del-1 and L1 play an important role in the process of tumor cells moving from the original place.