High levels of soluble intercellular adhesion molecule-1 (ICAM-1) in crevicular fluid of periodontitis patients with plaque

Abstract. The intercellular adhesion tnolecule-1 (ICAM-1) is a membrane-bound molecule involved in cell-cell adhesive interactions which is upregulated on inflammatory epithelial cells. The levels of soluble ICAM-1 (sICAM-1) shed into the gingival crevicular fluid (GCF) were studied in healthy patients and patients with gingivitis, adult periodontitis or rapidly progressive periodontitis, using an ELISA technique. Clinical parameters including plaque index, gingival index, probing depth, and bleeding on probing were recorded following careful sampling of GCF with standardised filter strips. In GCF, sICAM-1 levels were higher for patients with plaque ( p =0.04) and for patients with inflammation ( p =0.02), but did not correlate with disease classifications. These results suggest that elevated GCF sICAM-1 levels may represent increased shedding of this molecule in the interstitial fluid as a result of membrane-bound ICAM-1 upregulation on ICAM-1 gingival-bearing cells in relation with plaque accumulation and inflammation.     

Prostaglandin F2 alpha upregulates intercellular adhesion molecule-1 expression in human gingival fibroblasts

Prostaglandin F2 alpha (PGF2 alpha) is a bioactive lipid mediator, which has been suggested to be involved in the pathogenesis of periodontal disease. However, the roles of PGF2 alpha in the disease are not well understood. In the present study, we investigated the effect of PGF2 alpha on intercellular adhesion molecule-1 (ICAM-1) expression in human gingival fibroblasts (HGF) and the effect of PGF2 alpha on ICAM-1 expression elicited by proinflammatory cytokines, interferon-gamma (IFN-gamma) and tumour necrosis factor alpha (TNF alpha) in the cells. PGF2 alpha-stimulated HGF expressed ICAM-1 expression in a time- and dose-dependent manner. IFN-gamma-elicited ICAM-1 expression was synergistically increased by PGF2 alpha, whereas TNF alpha-induced ICAM-1 expression was slightly inhibited by PGF2 alpha. Fluprostenol, a selective FP receptor agonist, could mimic PGF2 alpha-induced effect on ICAM-1 expression. Furthermore, signal transduction for the regulation of ICAM-1 by PGF2 alpha was investigated using N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7), a calcium calmodulin antagonist, and 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H-7), an inhibitor of protein kinase C (PKC). W-7 and H-7, remarkably, suppressed PGF2 alpha-induced ICAM-1 expression and synergistic increase of ICAM-1 expression by combination of PGF2 alpha and IFN-gamma, while IFN-gamma-elicited ICAM-1 expression was only partially inhibited by W-7 and H-7. From these data, we suggest that PGF2 alpha upregulates ICAM-1 expression in HGF and synergistically enhances IFN-gamma-induced ICAM-1 expression through FP receptor by calcium calmodulin-dependent and PKC-dependent pathways. PGF2 alpha may be involved in the pathology of periodontal disease by upregulating ICAM-1 expression in HGF.     

CD99 ligation induces intercellular cell adhesion molecule-1 expression and secretion in human gingival fibroblasts

ObjectiveTo examine CD99 expression and its functional role in ICAM-1 induction in human gingival fibroblasts (HGFs) and human gingival epithelial cells (HGECs) by activating cells with anti-CD99 monoclonal antibody, MT99/3.BackgroundEngagement of CD99 with agonistic antibodies has been shown to regulate immune responses, cell adhesion and migration, and cell death in several studies. Particularly, this engagement results in transendothelial migration of leukocytes mediated by intercellular adhesion molecule-1 (ICAM-1) induction in endothelial cells.MethodsTotal mRNA and protein were isolated from HGFs and HGECs for analyses of CD99 and ICAM-1 expression. Surface expression of CD99 and ICAM-1 was analysed by flow cytometry, and the detection of soluble ICAM-1 was assayed by immunoprecipitation and ELISA.ResultsCD99 surface expression was constitutive on HGFs to a greater extent than that on HGECs. CD99 ligation with MT99/3 induced ICAM-1 mRNA expression in HGFs, but not in HGECs. Interestingly, CD99 ligation led to an increased level of soluble ICAM-1 detected in culture supernatant, whereas interleukin-1β (IL-1β) treatment induced expression of membrane-bound ICAM-1. Furthermore, ICAM-1 induction by CD99 engagement was demonstrated to involve the activation of the p50 subunit of nuclear factor-kappaB (NF-κB), extracellular signal-regulated kinase, and p46 c-Jun N-terminal kinase that differed from that by IL-1β treatment.ConclusionOur study has shown the involvement of CD99 ligation in the up-regulation of ICAM-1 expression and its secretion in gingival fibroblasts, which may be essential for better understanding of the pathogenesis of periodontal disease.     

Concentration of interleukin-1beta and neutrophil elastase activity in gingival crevicular fluid during experimental gingivitis

BACKGROUND, AIM: The aim of the present study was to measure interleukin-1beta concentrations and neutrophil elastase activity in gingival crevicular fluid (GCF) during experimental gingivitis in humans. MATERIAL AND METHODS: 12 healthy young men participated. After prophylaxis, they performed optimal hygiene to reach plaque and gingivitis indices of or approaching zero. All oral hygiene measures were then ceased for a period of 18 days. The Quigley-Hein plaque index (PLI) and Saxer & Mühlemann papillary bleeding index (PBI) were assessed. GCF samples were taken from the mesiobuccal site of two contralateral teeth in the upper jaw by means of periopapers at baseline and on days 3, 7, 14 and 18. After measuring the gingival crevicular fluid volume (GCFV) with the Periotron 8000, the samples were analyzed in our laboratory for the detection of IL-1beta concentration by ELISA. RESULTS: PLI and PBI showed a reduction prior to baseline reaching almost zero, both increasing from day 0 to day 18 (PLI=from 0.1 to 2.9, PBI=from 0 to 2.0). IL-1beta concentration increased from 229.25 ng/ml (day 0) to 526.13 ng/ml (day 18). Clinical data and IL-1beta concentrations were correlated with elastase activity (EA). No significant correlation could be demonstrated between the clinical parameters assessed and IL-1beta or EA (Spearman rank correlation coefficient). A correlation between GCFV and PBI from day 0 to day 18 could be demonstrated. CONCLUSION: Overall, both IL-1beta and EA showed an increase from baseline throughout the whole study.     

Levels of TGFbeta1 in gingival crevicular fluid during a 21-day experimental model of gingivitis

OBJECTIVE: TGFbeta1 is a multifunctional growth factor with both pro- and anti-inflammatory properties. This study aimed to determine levels of TGFbeta1 in gingival crevicular fluid (GCF), serum and plasma in the early stages of gingival inflammation. DESIGN: A 21-day experimental model of gingivitis employing a split mouth design with a soft vinyl splint used to cover test teeth during brushing. SUBJECTS: Ten healthy volunteers (mean age 21 years; five males and five females). METHODS: GCF and blood (with and without EDTA) was collected on days 0, 7, 14 and 21. GCF volumes were measured on a precalibrated Periotron 8000TM. Clinical indices of gingival inflammation and plaque levels were obtained after GCF sampling. Normal brushing resumed after GCF collection on day 21 and final samples were collected on day 35. TGFbeta1 and alkaline phosphatase (ALP) levels were determined using enhanced chemiluminescent methods. RESULTS: Clinical indices and GCF volumes increased at test sites during the 21-day test period. Concentrations of TGFbeta1 and ALP in GCF (test and control), serum and plasma did not change throughout the study (P > 0.3). However, total amounts of TGFbeta1 (pg sample-1) and ALP (mu IU sample-1) in GCF increased at test sites and were significantly higher than baseline values at days 7, 14 and 21 (P < 0.04). Control sites showed no variation in TGFbeta1 or ALP levels throughout the study period (P > 0.35). All parameters at test sites returned to control levels at day 35 (P > 0.3). CONCLUSION: The data indicate that GCF TGFbeta1 levels increase early in plaque-induced inflammation. Whether the biological consequence of this site-specific increase is pro- or anti-inflammatory in nature remains to be elucidated.     

Differential expression of interleukin-8 and intercellular adhesion molecule-1 by human gingival epithelial cells in response to Actinobacillus actinomycetemcomitans or Porphyromonas gingivalis infection

Little is known regarding the molecules expressed by gingival epithelial cells that are involved in initiating and maintaining inflammation following the interaction with periodontal pathogens. Thus, we investigated the effect of Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis infection on the expression of neutrophil chemoattractant interleukin 8 (IL-8) and the adhesion molecule intercellular adhesion molecule-1 by gingival epithelial cells. The data revealed that both IL-8 and intercellular adhesion molecule-1 expression increased after infection with A. actinomycetemcomitans (IL-8: 2- to 7-fold; intercellular adhesior molecule-1: 2.5- to 3.7-fold). IL-8 secretion reached a maximal level 6 h after the infection and the expression subsequently decreased to basal level. The increased cell surface intercellular adhesion molecule-1 expression started at 4 h after infection and reached a maximal level 14 h after the infection. In contrast, the expression of both molecules rapidly decreased 2 h after challenge with P. gingivalis. This opposite influence of A. actinomycetemcomitans and P. gingivalis infection on the expression of IL-8 and intercellular adhesion molecule-1 by gingival epithelial cells suggests that A. actinomycetemcomitans infection may initiate the recruitment of neutrophils, whereas the P. gingivalis infection may retard this process and therefore demonstrate a distinct perspective of virulence.     

不同fimA基因型牙龈卟啉单胞菌对人脐静脉内皮细胞产生血管细胞黏附分子1和细胞间黏附分子1的影响

目的 观察不同fimA基因型牙龈卟啉单胞菌(Porphyromonas gingivalis,Pg)对人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVEC)产生血管细胞黏附分子1(vascular cell adhesion molecule-1,VCAM-1)和细胞间黏附分子1(intercellular adhesion molecule-1,ICAM-1)的影响,探讨Pg在动脉粥样硬化发生、发展中的可能作用.方法 实验分别以PgATCC33277 (Ⅰ fimA ) 、WCSP115 (Ⅱ fimA)、W83 (Ⅳ fimA)和大肠杆菌脂多糖刺激HUVEC作为T1、T2、T3组(3个实验组)和阳性对照组,未受刺激的HUVEC作为阴性对照组;标准条件下厌氧培养上述3型Pg,将其以及大肠杆菌脂多糖分别与 HUVEC共同孵育2、6、24 h,采用流式细胞术检测HUVEC表面ICAM-1和VCAM-1的蛋白表达量,并通过激光共聚焦显微镜观察ICAM-1和VCAM-1的表达分布情况.结果 Ⅰ、Ⅱ、Ⅳ fimA型Pg刺激HUVEC后,细胞表面ICAM-1表达均增强(P<0.05),2、6、24 h表达量分别为Ⅰ fimA:60.27±5.43、80.81±1.44、85.94±2.56;Ⅱ fimA:86.69±8.81、90.19±0.00、96.18±0.48,Ⅳ fimA:59.66±0.40、85.79±4.86、96.04±2.07.除2 h时ⅠfimA与Ⅳ fimA型Pg刺激的HUVEC表面ICAM-1表达量差异无统计学意义外,其他各时间点Ⅱ、Ⅳ fimA型Pg的刺激作用均强于Ⅰ fimA型Pg(P<0.05).本研究条件下,Ⅰ、Ⅱ、Ⅳ fimA型Pg刺激HUVEC后2、6、24 h表达VCAM-1的水平均较低,各实验组与对照组间相比差异均无统计学意义(P>0.05).激光共聚焦显微镜观察显示,Pg刺激下HUVEC表达ICAM-1和VCAM-1增加,在Ⅱ、Ⅳ fimA型Pg刺激下,HUVEC中ICAM-1和VCAM-1荧光点相对较多且分布范围广.结论 牙周主要致病菌Pg毒力和致病性与其fimA基因型相关,Ⅱ fimA和Ⅳ fimA型Pg 有较强的上调HUVEC表达细胞黏附分子的能力,可能导致血管内皮功能紊乱.

Abstract：

Objective To investigate the effect of Porphyromonas gingivalis(Pg) with different fimA genotypes on vascular cell adhesion molecule-1(VCAM-1) and intercellular adhesion molecule-1(ICAM-1) production by human umbilical vein endothelial cells(HUVEC). Methods In the present study, PgATCC33277(type Ⅰ fimA genotype), WCSP 115(type Ⅱ fimA genotype), W83(type Ⅳ fimA genotype), and Escherichia coli-lipopolysaccharide (Ec-LPS) were designed as experimental group 1, 2, 3, and positive control group, respectively, to stimulate HUVEC, and the un-stimulated HUVEC were analyzed as negative control group. The three strains of Pg were cultured anaerobically in standard condition, and then the Pg cells and Ec-LPS were co-cultured with HUVEC for 2, 6, and 24 h, respectively. The amount of ICAM-1 and VCAM-1 produced by HUVEC was detected with flow cytometry(FCM). The expression of ICAM-1 and VCAM-1 by HUVEC were assayed with confocal laser scanning microscope(CLSM). ResultsThe expression of ICAM-1 on the surface of HUVEC were intensified after infected by Pg with Ⅰ, Ⅱ, and Ⅳ fimA genotypes (P<0.05). The amounts of ICAM-1 were 60.27±5.43, 80.81±1.44, and 85.94±2.56 for Pg with type Ⅰ fimA genotype, 86.69±8.81, 90.19±0.00, and 96.18±0.48 for Pg with type Ⅱ fimA genotype, 59.66±0.40, 85.79±4.86, and 96.04±2.07 for Pg with type Ⅳ fimA genotype at 2, 6 and 24 h after infection, respectively. The up-regulation effects caused by Pg with type Ⅱ and Ⅳ fimA genotypes were stronger than those caused by Pg with type Ⅰ fimA genotype at different time points except at 2 h(P<0.05). Under the present experimental condition, infected by Pg with type Ⅰ, Ⅱ and Ⅳ fimA genotypes stimulated low expression of VCAM-1 by HUVEC, it showed no significant differences among all the groups (P>0.05). Expression of ICAM-1 and VCAM-1 in Pg infected HUVEC were confirmed by CLSM. Infection of HUVEC with Pg resulted in more fluorescence staining of ICAM-1 and VCAM-1 compared with that in uninfected HUVEC cultures. Conclusions The virulence and pathogenicity of Pg is associated with its fimA genotypes, Pg with type Ⅱ and Ⅳ fimA genes possess stronger ability to stimulate HUVEC to up-regulate the expression of cell adhesion molecules, which may lead to disorders in vascular endothelial function.     

Experimental gingivitis in type 1 diabetics: a controlled clinical and microbiological study

OBJECTIVE: To monitor clinical and microbiological changes during experimental gingivitis in type 1 diabetics and non-diabetics. MATERIALS AND METHODS: Nine type 1 diabetics with good/moderate metabolic control and nine age-gender matched non-diabetics were recruited. Probing pocket depths in all subjects did not exceed 4 mm and none were affected by attachment loss. According to the original model, an experimental 3-week plaque accumulation resulting in experimental gingivitis development and a subsequent 2-week period of optimal plaque control were staged. Subgingival plaque samples were collected at days 0, 21 and 35 from one site per quadrant, pooled and analysed using checkerboard DNA-DNA hybridization. RESULTS: Diabetics (mean age 25.6+/-5.8 standard deviation (SD), range 16-35 years) had a mean HbA1c level of 8.1+/-0.7% (SD), while non-diabetics (mean age 24.8+/-5.7 (SD), range 15-36 years) were metabolically controlled (HbA1c< or =6.5%). Between Days 0, 21 and 35, no statistically significant differences in mean plaque and gingival index scores were observed between diabetics and non-diabetics. At days 7 and 21, however, diabetics showed statistically significantly higher percentages of sites with gingival index scores > or =2 compared with non-diabetics. Mean DNA probe counts of the red and orange complex species increased significantly (p<0.05) between days 0 and 21 and decreased significantly (p<0.05) between days 21 and 35 in both groups. CONCLUSION: Both diabetics and non-diabetics react to experimental plaque accumulation with gingival inflammation. Type 1 diabetics, however, develop an earlier and higher inflammatory response to a comparable bacterial challenge.     

Prostaglandin E2 and I2 regulate intercellular adhesion molecule-1 expression in interleukin-1 beta-stimulated human gingival fibroblasts

The present study investigated the effect of prostaglandin (PG) E₂ and PGI₂ on intercellular adhesion molecule-1 (ICAM-1) expression in interleukin-1β (IL-1β)-stimulated human gingival fibroblasts (HGF). IL-1β potently induced ICAM-1 expression in HGF and indomethacin, a cyclooxygenase inhibitor, enhanced ICAM-1 expression in the cells. These data showed that endogenous PGs generated by HGF stimulated with IL-1β downregulated ICAM-1 expression. IL-1β significantly increased the levels of PGE₂ and, to a lesser extent, those of 6-keto-PGF_1α (a stable metabolite of PGI₂) in the culture media of HGF. Indomethacin completely inhibited the production of PGE₂ and 6-keto-PGF_1α in IL-1β-stimulated HGF. Exogenous PGE₂ and carbacyclin (a stable derivative of PGI₂) in the presence of indomethacin dose-dependently suppressed ICAM-1 expression in IL-1β-challenged HGF. Since PGE₂ and PGI₂ are known to elevate intracellular cyclic AMP (cAMP) levels, we examined the effect of dibutyryl cAMP, a cAMP analogue, and isobutylmethylxanthine, a phosphodiesterase inhibitor, on ICAM-1 expression. Both agents downregulated ICAM-1 expression in IL-1β-stimulated HGF. These results suggest that PGE₂ and PGI₂ downregulate ICAM-1 expression in IL-1β-stimulated HGF through a cAMP-dependent mechanism and that intracellular cAMP elevation in HGF may control inflammatory and immune responses in periodontal disease.     

Protease-activated receptor 2 mediates interleukin-8 and intercellular adhesion molecule-1 expression in response to Aggregatibacter actinomycetemcomitans

Introduction:  We investigated the mechanisms by which extracts of Aggregatibacter actinomycetemcomitans affect the inflammatory response in gingival epithelial cells.
Methods:  Human gingival cells (Ca9-22) were cultured in bacterial extracts prepared from A.   actinomycetemcomitans ATCC 29522. The cells were pretreated with protease inhibitors or transfected with small interfering RNA (siRNA) specific for protease-activated receptor 2 (PAR-2).
Results:  The pretreatment of cells with serine protease inhibitors significantly inhibited A.   actinomycetemcomitans extract-induced expression of interleukin-8 (IL-8) and intercellular adhesion molecule-1 (ICAM-1) at both the messenger RNA and protein levels. In addition, A. actinomycetemcomitans extract-induced IL-8 and ICAM-1 expression was significantly decreased in PAR-2/siRNA-transfected cells.
Conclusions:  A. actinomycetemcomitans extract-induced IL-8 and ICAM-1 expression in gingival epithelial cells is mediated by PAR-2.     

正畸移动牙龈沟液中IL-1βICAM-1的表达

目的 探讨成人牙齿受到正畸力后龈沟液中白细胞介素-1和可溶性细胞粘附分子-1(sICAM-1)的表达.方法 选择27例已拔除双侧上颌第一前磨牙的患者,用弹簧施力于其一侧上颌尖牙向远中,为实验组;对侧不受力,为对照组.分别于施力前、施力后1、2、3、7、21、28天用ELISA法检测双侧上颌尖牙龈沟液(GCF)中IL-1夂蛃ICAM-1的含量.结果 实验组在受力后龈沟液中IL-1夂蛃ICAM-1均开始升高,第3天达到高峰,第28天基本回落至基线.对照组GCF中IL-1夂蛃ICAM-1基本维持在基线.第2、3天实验组GCF中IL-1獾暮亢偷、3、7天sICAM-1的含量与对照组相比有显著性差异(P＜0.05).结论 在正畸过程中,牙齿GCF中IL-1夂蛃ICAM-1的表达随牙周组织的受力改变而发生动态变化,与牙齿移动和牙槽骨重建有关,可作为一种临床检测方法.     

Expression of the CD54 (ICAM-1) and CD11 a (LFA-1) adhesion molecules in oral mucosal inflammation

Previous studies of chronic dermatoses have suggested that expression of the CD54 cell surface antigen (intercellular adhesion molecule-1, ICAM-1) by keratinocytes is a feature of chronic inflammation. However, whether such expression is a prerequisite for intraepithelial migration of lymphocytes is unclear. The present study evaluated the expression of CD54 and its ligand, CD1 la (lymphocyte function-associated antigen, LFA-1) in oral lesions of lichen planus, recurrent aphthous stomatitis, secondary Sjögren's syndrome and traumatic ulceration using an immunoperoxidase technique. In 33 of 56 lesions examined, substantial numbers of CD1 la + cells were present within oral mucosal epithelium despite an absence of detectable keratinocyte CD54 antigen expression. Consequently, CD54/CD1 la adhesion interactions may not be critical in the initiation of oral mucosal inflammation.     

不同金属烤瓷全冠对龈沟液内可溶性细胞间黏附分子-1及白细胞介素-1β水平的影响

目的 通过对不同内冠金属材料的烤瓷熔附金属(PFM)全冠修复后龈沟液(GCF)内可溶性细胞间黏附分子-1 (sICAM-1)及白细胞介素-1β(IL-1β)水平的测定,探讨内冠金属材料对牙周组织的影响.方法 将30颗牙分为镍铬合金组、钴铬合金组和金铂合金组,每组10颗,分别进行镍铬合金、钴铬合金和金铂合金PFM全冠修复...     

牙龈卟啉单胞菌感染对大鼠血管平滑肌细胞细胞间黏附分子-1表达的影响

目的 观察牙龈卟啉单胞菌ATCC 33277感染对大鼠血管平滑肌细胞（VSMC）细胞间黏附分子-1（ICAM-1）表达的影响。方法 建立体外牙龈卟啉单胞菌感染大鼠VSMC模型,逆转录-聚合酶链反应（RT-PCR）检测ICAM-1基因的表达。结果 牙龈卟啉单胞菌感染VSMC 8、16、24 h后,ICAM-1表达明显增多,与空白对照组比较,差异有统计学意义（P<0.05）。感染16 h达高峰,感染8 h与感染16、24 h比较,差异有统计学意义（P<0.05）。结论 牙龈卟啉单胞菌感染可引起VSMC ICAM-1高表达,这提示牙周致病菌可能参与血管壁的炎症反应,在动脉粥样硬化的发生、发展中有重要的意义。     

一氧化碳对肿瘤坏死因子-α和白细胞介素-1β共同诱导的人牙龈成纤维细胞黏附分子表达的影响

目的研究一氧化碳对炎性环境下人牙龈成纤维细胞黏附分子表达的影响。方法以50 ng·mL-1的肿瘤坏死因子（TNF）-α和10 ng·mL-1的白细胞介素（IL）-1β刺激加入或不加入500 μmol·L-1一氧化碳释放分子（CORM）的人牙龈成纤维细胞,用Western blot法检测细胞间黏附分子（ICAM）-1、血管细胞黏附分子（VCAM）-1的蛋白表达,用逆转录多聚酶链反应（RT-PCR）检测黏附分子的mRNA表达,用瞬时转染和报告基因测定法分析NF-κB的活性。结果TNF-α和IL-1β共同刺激后,人牙龈成纤维细胞ICAM-1和VCAM-1的mRNA表达和蛋白表达均显著增强。CORM的加入可显著抑制ICAM-1和VCAM-1的表达。CORM可显著降低ICAM-1和VCAM-1诱导的NF-κB的活性。结论一氧化碳有可能成为牙周病治疗的一种极具潜力的新物质。     

血管细胞黏附分子-1在口腔鳞状细胞癌中的表达及其意义

目的研究血管细胞黏附分子-1（VCAM-1）在口腔鳞状细胞癌（OSCC）中的表达与定位及其临床意义。方法应用分子原位杂交和免疫组化方法对48例OSCC组织和10例正常口腔黏膜组织中VCAM-1 mRNA和VCAM-1蛋白质的表达和定位进行检测,比较VCAM-1在不同口腔组织中的表达率及其与临床指标的关系。结果VCAM-1蛋白定位于肿瘤细胞胞浆和胞膜,VCAM-1 mRNA定位于肿瘤细胞胞浆。VCAM-1 mRNA和VCAM-1蛋白在OSCC中的表达率均显著高于正常口腔黏膜组织（P＜0.01）,VCAM-1 mRNA表达与VCAM-1蛋白表达呈正相关（P＜0.01）;OSCC中淋巴结转移者VCAM-1蛋白的表达显著高于无淋巴结转移者（P＜0.01）。结论OSCC中VCAM-1基因的高表达可能与肿瘤的浸润和转移有关。