舌癌组织中淋巴管密度与淋巴道转移关系的研究

目的：研究舌癌组织中淋巴管密度（lymphatic vessel density,LVD）和舌鳞状细胞癌患者淋巴道转移的相关性。方法：舌癌样本来自138例实施舌癌切除术的患者。利用单克隆抗体D2-40进行免疫组织化学染色。对照正常组织和肿瘤组织中LVD的差异。利用Spearman相关分析评估舌癌患者的LVD和临床病理因素的联系。结果：舌癌组织中LVD明显高于正常组织（P〈0.01）。已发生转移的肿瘤组织中LVD明显高于未转移肿瘤组织（P〈0.01）。LVD与舌癌患者T分期、分级、淋巴结状态和临床分期（r=0.229,0.221,0.794,0.740）具有紧密联系。结论：LVD有规律的增长可能是舌癌发展的一个重要特征,有助于预测舌癌患者早期的淋巴转移。     

Computer‐assisted morphometric analysis of lymphatic vessel changes in hamster tongue carcinogenesis

J Oral Pathol Med (2010) 39 : 518–524 Background: To characterize lymphangiogenesis in early‐stage hamster tongue carcinoma development, morphological features and spatial relationships of lymphatic vessels. Methods: Lymphatic vessels were examined histochemically, using 5′‐Nase‐ALPase enzyme and combined light and electron microscopy to measure lymphatic vessel area (LVA) and lymphatic vessel density (LVD). Results: In atypical hyperplastic tissues, LVA was found to be 1429.97 and LVD was found to be 39, in carcinoma in situ LVA was 2538.33 and LVD was 48, and in micro‐invasive carcinoma LVA was 5733.74 and LVD was 59. Increased lymphangiogenesis was seen in pre‐neoplastic states and in early‐stage oral squamous cell carcinoma (OSCC). Small regular lymphatic vessels predominated in atypical hyperplasia, and large, irregular lymphatic vessels in early‐stage OSCC. Lymphatic endothelial vessels were stretched and porous over large areas. Conclusions: Newly formed lymphatics and patulous intercellular junctions may be optimally suited for tumor cell metastasis through lymphatic channels in early‐ and middle‐phase carcinogenesis. Lymphatic capillary LVA and LVD became enlarged, and positively correlated, with malignancy, but show no correlation with 7,12‐dimethylbenz[a]anthracene‐induced time.     

Podoplanin在口腔鳞状细胞癌中的表达及与淋巴结转移的关系

目的:采用淋巴管特异性标志物podoplanin标记口腔鳞癌组织和正常口腔组织中的淋巴管,并计数淋巴管密度(lymphatic vessel density,LVD)值,探讨口腔鳞癌及癌周淋巴管密度与淋巴结转移的相关性及可能机制。方法:采用免疫组织化学方法检测21例正常口腔黏膜组织和88例口腔鳞癌患者组织的podoplanin表达;用podoplanin标记淋巴管,并计数口腔鳞癌和癌周组织的淋巴管密度。采用SPSS13.0软件包对数据进行t检验,分析正常组织和癌组织、淋巴结转移组和未转移组的淋巴管密度(癌周、癌内)。结果:口腔鳞癌及癌周组织的淋巴管密度均高于正常口腔黏膜组织,有显著差异(P<0.05)。癌组织内淋巴管小而闭锁,癌组织周围的淋巴管大而扩张;淋巴结转移组的癌周淋巴管密度(14.270±4.610)显著高于无转移组(9.450±2.411),差异具有显著性(P<0.05),癌组织淋巴管密度在2组间无显著差异。结论:口腔鳞癌患者癌周淋巴管的生成可能是影响区域淋巴结转移的重要因素。     

口腔鳞癌中血管内皮生长因子C、受体3和抑癌基因nm23-H1的表达及意义

目的探讨血管内皮生长因子C（vascular endothelial growth factor C，VEGF-C）、受体3（vascular endothelial growth factor receptor-3，VEGFR-3）和抑癌基因nm23-H1的表达在口腔鳞状细胞癌（oral squamous cell carcinoma，OSCC）淋巴转移中的作用。方法对经病理证实的OSCC60例切片采用免疫组化SP法检测VEGF-C、VEGFR-3和nm23-H1的表达，计数肿瘤淋巴管密度（lymphatic vessels density，LVD），结合临床病理因素进行分析。结果OSCC中VEGF-C蛋白阳性率为58．3％，LVD为（8．43±2．64）个／高倍镜下和nm23-H。阳性表达，三者均明显差异于癌前病变和良性病变（P〈0．05），VEGF-C表达和LVD、淋巴结转移相关（P〈0．01）；nm23-H1表达与淋巴结转移、临床分期和组织学分级相关（P〈0．05）。结论在OSCC淋巴转移中VEGF-C、VEGFR-3高表达和nm23-H1蛋白缺失起重要作用，三者的检测结果对深入探讨肿瘤淋巴转移机制有参考价值。     

口腔癌淋巴管密度检测及其临床意义

目的探讨口腔癌组织中淋巴管密度（LVD）与颈淋巴结转移及其它临床病理参数之间的关系。方法选择56例口腔鳞状细胞癌石蜡组织标本，采用免疫组化方法检测淋巴管内皮标志物D2-40及淋巴管内皮透明质酸受体-1（LYVE-1）在口腔癌中的表达，计算口腔癌中的LVD，并进行统计学分析，观察LVD与颈淋巴结转移及其它临床病理参数（性别、年龄、发病部位、T分期、病理分级、浸润方式）之间的关系。结果LYVE-1染色显示，癌内LVD在淋巴结转移组明显高于无转移组（P〈0．05）。LYVE-1染色和D2-40染色均显示癌内LVD与病理分级呈正相关（P〈0．017）。LVD与性别、年龄、发病部位、T分期及浸润方式均无关。结论对于口腔癌来说，癌内淋巴管在肿瘤的浸润和转移中发挥重要作用。     

Role of lipocalin 2 and its complex with matrix metalloproteinase-9 in oral cancer

Oral Diseases (2012) 18 , 734–740 Objectives: Recent evidence demonstrated that lipocalin (LCN)2 is induced in many types of human cancer, while the detection of its complex with matrix metalloproteinase (MMP)‐9 is correlated with the cancer disease status. We attempted to evaluate plasma expressions of LCN2, MMP‐9, and their complex (LCN2/MMP‐9) during the diagnostic work‐up of patients with oral squamous cell carcinoma (OSCC) and investigated their correlations with disease progression. Methods: In total, 195 patients with OSCC and 81 healthy controls were recruited. Expression levels of LCN2, MMP‐9, and LCN2/MMP‐9 were determined with immunoenzymatic assays. Results: Patients with OSCC exhibited significantly higher levels of LCN2, MMP‐9, and LCN2/MMP‐9 compared with healthy controls (LCN2: P < 0.001; MMP‐9: P < 0.001; LCN2/MMP‐9: P < 0.01). Plasma levels of LCN2, MMP‐9, and LCN2/MMP‐9 in patients with OSCC were significantly correlated with each other and were associated with more‐advanced clinical stages (P < 0.05) and/or a larger tumor size (P < 0.05), but were not associated with positive lymph‐node metastasis or distal metastasis. Conclusion: Our results suggest that plasma levels of LCN2 and the LCN2/MMP‐9 complex may be useful in non‐invasively monitoring OSCC progression, while supporting their potential role as biomarkers of oral cancer disease status.     

Immunohistochemical analysis of lymphatic vessel density and mast cells in oral tongue squamous cell carcinoma

The aim of this study was to analyze lymphangiogenesis and the presence of mast cells in oral tongue squamous cell carcinoma (OTSCC), correlating the findings with clinicopathological parameters (clinical stage, tumor size, nodal metastasis, histological grade of malignancy, local recurrence, and clinical outcome). Fifty-six cases of primary OTSCC were selected. Lymphatic vessels and mast cells were identified by immunostaining with anti-podoplanin (D2-40) and anti-tryptase antibody, respectively. Lymphatic vessel density (LVD) and mast cell density (MCD) were determined in the intratumoral and peritumoral areas. Intratumoral LVD was higher in advanced clinical stages (III/IV) when compared to early-stage (p = 0.017) and in metastatic cases compared to non-metastatic tumors (p = 0.013). Peritumoral LVD and intratumoral or peritumoral MCD did not differ significantly according to the clinicopathological parameters of OTSCCs (p > 0.05). No significant correlations between LVD and MCD were observed at the intratumoral (r = ?0.014; p = 0.918) or peritumoral level (r = 0.156; p = 0.251). Our findings suggest that intratumoral lymphatic vessels, compared to peritumoral lymphatic vessels, appear to be more related to the progression of OTSCC. MCD alone does not seem to be determinant for lymphangiogenesis or for the biological behavior of OTSCC, indicating multiple pro- and antitumor effects of these inflammatory cells.     

Endothelial cell Bcl-2 and lymph node metastasis in patients with oral squamous cell carcinoma

J Oral Pathol Med (2012) 41 : 124–130 Background: Loco‐regional spread of disease causes high morbidity and is associated with the poor prognosis of malignant oral tumors. Better understanding of mechanisms underlying the establishment of lymph node metastasis is necessary for the development of more effective therapies for patients with oral cancer. The aims of this work were to evaluate a possible correlation between endothelial cell Bcl‐2 and lymph node metastasis in patients with oral squamous cell carcinoma (OSCC), and to study signaling pathways that regulate Bcl‐2 expression in lymphatic endothelial cells. Methods: Endothelial cells were selectively retrieved from paraffin‐embedded tissue sections of primary human OSCC from patients with or without lymph node metastasis by laser capture microdissection. RT‐PCR was used to evaluate Bcl‐2 expression in tumor‐associated endothelial cells and in tumor cells. In vitro, mechanistic studies were performed to examine the effect of vascular endothelial growth factor (VEGF)‐C on the expression of Bcl‐2 in primary human lymphatic endothelial cells. Results:  We observed that Bcl‐2 expression is upregulated in the endothelial cells of human oral tumors with lymph node metastasis as compared to endothelial cells from stage‐matched tumors without metastasis. VEGF‐C induced Bcl‐2 expression in lymphatic endothelial cells via VEGFR‐3 and PI3k/Akt signaling. Notably, OSCC cells express VEGF‐C and induce Bcl‐2 in lymphatic endothelial cells. Conclusions: Collectively, this work unveiled a mechanism for the induction of Bcl‐2 in lymphatic endothelial cells and suggested that endothelial cell Bcl‐2 contributes to lymph node metastasis in patients with oral squamous cell carcinoma.     

Prognostic significance of matrix metalloproteinase-2, -8, -9, and -13 in oral tongue cancer

J Oral Pathol Med (2012) 41 : 394–399 Background: Oral tongue squamous cell carcinoma (OTSCC) often metastasizes to cervical lymph nodes. Mechanisms of this disease progression are not fully known. We aimed at finding new predictive markers for diagnosis and disease monitoring. Methods: Seventy‐three consecutive T1N0M0 and T2N0M0 OTSCC patients treated at Helsinki University Central Hospital, Helsinki, Finland, in 1992–2002 were included. Tissue array blocks were prepared from primary tumors and immunostained. Immunoexpression of matrix metalloproteinase (MMP)‐2, ‐8, ‐9, and ‐13 was compared with patient characteristics and outcome. Results: Nuclear expression of MMP‐13, but not cytoplasmic expression of MMP‐2, ‐8, and ‐9, was associated with invasion depth (P = 0.017) and tumor size (P = 0.008). Furthermore, high nuclear MMP‐13 expression was predictive of poor outcome (P = 0.042). Conclusion: Our results suggest that especially MMP‐13 may be regarded as a prognostic biomarker in OTSCC.     

VEGF-C的表达与口腔鳞癌淋巴结转移的关系

目的:观察口腔鳞癌中D2-40及VEGF-C的表达特点,探讨VEGF-C在肿瘤淋巴管生成及淋巴结转移中的作用。方法:将43例口腔鳞癌分为淋巴结转移组和无淋巴结转移组,应用免疫组织化学SP法检测D2-40及VEGF-C的表达情况。结果:口腔鳞癌中的淋巴管主要分布在肿瘤边缘区(肿瘤间质)。癌组织中淋巴管密度及VEGF-C的阳性表达率显著高于正常组织(P<0.05),淋巴结转移组癌灶中淋巴管密度及VEGF-C的阳性表达率显著高于无淋巴结转移组(P<0.05)。结论:口腔鳞癌肿瘤边缘区淋巴管与淋巴结转移相关,VEGF-C可能参与口腔鳞癌淋巴管的形成。     

口腔鳞状细胞癌中血管内皮生长因子-C的表达及其与血管、淋巴管生成、淋巴结转移的关系

目的探讨血管内皮生长因子-C（VEGF-C）在口腔鳞状细胞癌（OSCC）组织中的表达情况及其与血管、淋巴管生成、淋巴结转移之间的关系。方法调查拥有完整临床病理资料的67例口腔鳞癌患者的手术切除标本,采用SP免疫组化技术检测VEGF-C的表达情况并分析其与微血管密度（MVD）、淋巴管密度（LVD）及其他临床病理指标的关系。结果晚期病例、淋巴结转移阳性病例的VEGF-C表达明显升高（P值分别为0.015和<0.001）,而VEGF-C表达与患者性别、肿瘤部位、肿瘤分化程度无关（P>0.05）。VEGF-C高表达组的LVD明显高于VEGF-C低表达组（P=0.001）,但两组间MVD无统计学差异（P=0.125）。此外,淋巴结转移阳性组的LVD明显高于淋巴结转移阴性组（P=0.026）。结论VEGF-C可能主要通过参与诱导口腔鳞癌淋巴管生成促进淋巴结转移。     

口腔鳞癌中MMP-1、MMP-2、uPA的表达与肿瘤侵袭和转移的关系

目的:探讨基质金属蛋白酶-1、2(MMP-1、MMP-2)、尿激酶型纤溶酶原激活物(uPA)在口腔鳞癌中的表达及与肿瘤侵袭和转移的关系。方法:采用免疫组织化学通用型两步法检测80例口腔鳞癌患者的癌旁正常组织和癌组织中MMP-1、MMP-2、uPA的表达。结果:口腔鳞癌组织中MMP-1、MMP-2、uPA的表达明显高于口腔癌旁正常组织(P<0.05)。中低分化鳞癌中MMP-1的表达明显高于高分化鳞癌(P<0.05),高分化鳞癌中MMP-1的表达明显高于癌旁正常组织(P<0.05);高分化鳞癌与中低分化鳞癌中MMP-2、uPA的表达明显高于癌旁正常组织(P<0.05),高分化鳞癌与中低分化鳞癌中MMP-2、uPA的表达水平基本一致(P>0.05)。MMP-1的表达与口腔鳞癌的T分期、生长部位无明显的相关性,与生长方式、病理学分级、临床分期、淋巴结状况有明显的正相关性(r分别是0.363、0.375、0.479、0.506);MMP-2的表达与口腔鳞癌的生长方式、生长部位、病理分级无明显的相关性,与T分期、临床分期、淋巴结状况有明显的正相关性(r分别是0.300、0.552、0.626);uPA的表达与口腔鳞癌的生长部位、病理分级无明显的相关性,与T分期、生长方式、临床分期、淋巴结状况有明显的正相关性(r分别是0.292、0.279、0.525、0.524)。结论:MMP-1、MMP-2、uPA的表达与口腔鳞癌的侵袭、转移关系密切,有望在临床上成为判断侵袭、转移指标。MMP-1是口腔鳞癌颈淋巴结转移的危险因子。     

Fos‐related activator‐1 is overexpressed in oral squamous cell carcinoma and associated with tumor lymph node metastasis

J Oral Pathol Med (2010) 39 : 470–476 Background: Previously, we established an in vitro cellular carcinogenesis model of oral squamous cell carcinoma (OSCC), including the human immortalized oral epithelia cells (HIOECs) and its derived cancerous HB cells. Then, expression microarray analysis showed that the gene encoding fos‐related activator‐1 (Fra‐1) was significantly upregulated in the cancerous HB cells compared with HIOECs. Methods: To confirm the expression of Fra‐1 at mRNA and protein levels by real‐time PCR and western blotting analysis in the carcinogenesis model of OSCC and CAL27 cells. To investigate Fra‐1 expression in clinical samples from 30 primary OSCC patients by immunohistochemistry. Results: Fra‐1 expression was increased both at mRNA and protein levels in this carcinogenesis model of OSCC and CAL27 cells. Nuclear and cytoplasmic Fra‐1 protein expressions both increased in the cancerous tissues compared with those in the paired adjacent non‐malignant epithelia (nuclear: P < 0.001, cytoplasmic: P = 0.003). A higher level of nuclear Fra‐1 expression was seen in the tumor samples of patients with lymph node metastasis than those without lymph node metastasis (5.07 ± 1.33 vs 3.81 ± 1.33, P = 0.023). Higher level of Fra‐1 expression was also found in the tumor invasive margin than tumor center. Conclusions: Fra‐1 is a positive gene of OSCC development and progression, Fra‐1 can be used as a potential therapeutic target gene and an additional marker for evaluation of lymph node metastasis.     

Intratumoral lymphangiogenesis in oral squamous cell carcinoma and its clinicopathological significance

Lymphatic metastasis has always been regarded as a major prognostic indicator for disease progression and as a guide for therapeutic strategies to oral squamous cell carcinoma (OSCC), but to date, how tumor cells access and spread via the lymphatics have not been fully elucidated. Whether tumor cells metastasize by expansion and invasion of pre‐existing peritumoral lymphatics or by the induction and invasion of newly formed lymphatics within tumors is controversial. In order to address this issue and find out the clinicopathological significance of intratumoral lymphangiogenesis, we investigated 86 archival specimens from patients with OSCC, quantitating lymph vessels by immunostaining with D2‐40. We also quantified lymphatic invasion and examined the possible associations of all the above parameters with clinicopathological features and outcome. Higher intratumoral lymphatic density (ILD) and peritumoral lymphatic density (PLD) were both significantly associated with the presence of lymph node metastasis at the time of diagnosis and the outcome of the post‐operation biopsy of 77 patients (P = 0.001). Higher ILD was significantly associated with a higher incidence of intratumoral lymphatic invasion, peritumoral lymphatic invasion and recurrence of tumor (P = 0.001 and P = 0.041 and P = 0.001, respectively). Patients with higher ILD exhibited shorter 5‐year cumulative and disease‐free survival (P = 0.001). Thus, lymphangiogenesis indeed occurs in oral squamous cell carcinoma; ILD might be used as an index to inflect the aggression of the disease, to evaluate the status of lymphatic metastasis, to separate patients at higher risk of an adverse clinical outcome.     

长链非编码RNA AFAP1-AS1在口腔鳞状细胞癌中的表达及临床意义

目的:探讨长链非编码RNA (lncRNA) 肌动蛋白纤维相关蛋白1-反义RNA1(AFAP1-AS1)在口腔鳞癌及癌旁组织中的表达及其临床意义。方法:利用实时定量PCR(RT-qPCR)法检测75例口腔鳞癌组织及其配对癌旁正常组织中lncRNA AFAP1-AS1的表达情况,并分析其与口腔鳞癌临床病理学特征之间的联系;应用小干扰RNA(siRNA)干扰lncRNA AFAP1-AS1表达,CCK-8实验检测lncRNA AFAP1-AS1对口腔鳞癌细胞株Tca8113细胞增殖能力的影响。结果:RT-qPCR检测结果显示lncRNA AFAP1-AS1在癌组织中的相对表达水平是癌旁组织的5.16倍,差异有统计学意义(P＜0.01)。lncRNA AFAP1-AS1的表达与临床分期、分化程度及淋巴结转移显著相关(P＜0.05)。CCK-8实验结果显示,转染48 h、72 h实验组A₄₅₀值较对照组显著降低(P＜0.01),表明siRNA沉默AFAP1-AS1表达后,抑制了Tca8113细胞的增殖。结论:lncRNA AFAP1-AS1在口腔鳞癌中的表达上调可能与口腔鳞癌的发生发展有关。     

口腔鳞状细胞癌组织中HIF—1α，VEGF-C的表达及与淋巴管生成的关系

目的：研究口腔鳞状细胞癌（Orals quamous cell carcinoma,OSCC）组织中乏氧诱导因子-1α（Hypoxiainducible factor-1α,HIF—1α）,血管内皮生长因子-C（vascular endothelial growth factor,VEGF-C）表达水平及微淋巴管密度（LVD）,探讨其临床病理意义及在口腔鳞状细胞癌中的相互关系。方法：应用免疫组织化学SP法检测65例口腔鳞状细胞癌中HIF-1α,VEGF—C,淋巴管内皮细胞透明质酸受体-1（Lymphatic vessel endothelial hyaluronic acid receptor--1,LYVE—1）的表达并计数LVD。结果：65例OSCC中有43例HIF-1α呈（66．2％）高表达,VEGF--C有34例（52．3％）高表达。HIF-1α和VEGF—C高表达的病例中都出现高淋巴管密度。HIF-1a高表达分别与VEGF--C高表达显著相关（P〈0．05,χ2检验）,与高淋巴管密度显著相关（P〈0．01,Mann—Whitneyu—test）,与区域淋巴结转移显著相关（P〈0.01,χ2检验）而且也同UICCTNM分期相关（P〈0．05,χ2检验）。结论：OSCC中HIF-1α可能通过上调VEGF—C的表达来诱导淋巴管生成并最终导致肿瘤细胞发生区域淋巴结转移。     

miR‐181 as a putative biomarker for lymph‐node metastasis of oral squamous cell carcinoma

J Oral Pathol Med (2011) 40 : 397–404 Background: Oral squamous cell carcinoma (OSCC) is an important malignant disease around the world. Aberrant expression of MicroRNAs (miRNAs) has been implicated in carcinogenesis of various cancers. In previous studies, up‐regulation of miR‐181 was observed when OSCC progressed from leukoplakia, dysplasia to invasive carcinoma. However, the function of miR‐181 in oral tumorigenesis remains unclear. Materials and methods: The expression levels of miR‐181 in the tissue and plasma of OSCC patients were measured by quantitative RT‐PCR. The correlation between miR‐181 level and multiple clinical variables were then checked by Mann–Whitney test and Wilcoxon matched pairs test. To study the functional meaning of up‐regulated miR‐181, migration assay and invasion assay by transwells and colony forming assay were applied to analyze the tumorigenic phenotypes of OSCC cells with ectopical expression of miR‐181. Results: Among different clinical variables, over‐expression of miR‐181 was correlated with lymph‐node metastasis, vascular invasion, and a poor survival. Functional assays revealed ectopically over‐expressed miR‐181 would enhance cell migration and invasion, but not the ability of anchorage‐independent growth of OSCC cells. In addition, the up‐regulation of miR‐181 could be detected both in tumor tissues and plasma. Conclusion: miR‐181 may enhance lymph‐node metastasis through regulating migration, which could potentially be exploited as a putative biomarker for patients with OSCC.     

口腔鳞癌血管生成中MMP-2与巨噬细胞的关系

目的:探讨人类口腔鳞状细胞癌(OSCC)中基质金属蛋白酶-2(MMP-2)的表达并与肿瘤相关巨噬细胞(TAMs)以及微血管密度(MVD)间的关系。方法:采用免疫组化SABC法分别检测在42例口腔鳞癌和10例口腔正常组织中MMP-2的表达情况和CD68标记的巨噬细胞及CD34标记的MVD值。结果:口腔鳞癌中MMP-2的表达与淋巴结转移、TNM分期有关(P<0.05);MMP-2的表达与MVD值之间存在相关性(r=0.641,P<0.001),同时也与肿瘤内浸润的巨噬细胞相关(r=0.433,P<0.01)。结论:OSCC中的TAMs与MMP-2密切相关,TAMs可能通过MMP-2发挥促血管生成作用,促进肿瘤生长、发展和转移。     

Expression of osteonectin/secreted protein acidic and rich in cysteine and matrix metalloproteinases in ameloblastoma

J Oral Pathol Med (2010) 39 : 242–249 Background: Ameloblastoma is the most common clinically‐significant epithelial odontogenic tumor, and is considered a benign but locally‐aggressive tumor of the craniofacial region. Osteonectin/secreted protein acidic and rich in cysteine (SPARC) is induced in response to a number of biological processes such as tumor growth and metastasis, whereas matrix metalloproteinases (MMPs) degrade the extracellular matrix and participate in various biological processes including tumor invasion and metastasis. We hypothesize that SPARC acts with MMPs for the local invasiveness of ameloblastoma. The aim of this study was to examine the association of SPARC with MMP‐1, MMP‐2, and MMP‐9 in ameloblastoma. Method: Immunohistochemical expression of SPARC, MMP‐1, MMP‐2, and MMP‐9 as well as co‐expression of SPARC and MMP‐9 were examined in a cohort of 23 cases of ameloblastoma. Results: SPARC, MMP‐1, ‐2, and ‐9 were detected in the cytoplasm of the ameloblastic‐like columnar cells and stellate‐reticulum‐like cells as well as in the stromal tissues of fibroblasts and endothelial cells of our cohort of ameloblastoma patients. Furthermore, co‐expression of SPARC and MMP‐9 were found in 23 cases of ameloblastoma. This may be the first study to demonstrate that the expression level of SPARC was statistically correlated with MMP‐9 but not with MMP‐1 or ‐2 in ameloblastoma. Conclusion: Our results suggest a putative association between SPARC and MMPs (especially MMP‐9) in ameloblastoma to regulate tumor invasion.     

Oral cancer cells with different potential of lymphatic metastasis displayed distinct biologic behaviors and gene expression profiles

J Oral Pathol Med (2010) 39 168–175 Objective: Oral squamous cell carcinoma (OSCC) often spreads from the primary tumor to regional lymph nodes in the early stage. Better understanding of the biology of lymphatic spread of oral cancer cells is important for improving the survival rate of cancer patients. Methods: We established the cell line LNMTca8113 by repeated injections in foot pads of nude mice, which had a much higher lymphatic metastasis rate than its parental cell line Tca8113. Then, we compared the biologic behaviors of cancer cells between them. Moreover, microarray‐based expression profiles between them were also compared, and a panel of differential genes was validated using real‐time‐PCR. Results: In contrast to Tca8113 cells, LNMTca8113 cells were more proliferative and resistant to apoptosis in the absence of serum, and had enhanced ability of inducing capillary‐like structures. Moreover, microarray‐based expression profiles between them identified 1341 genes involved in cell cycle, cell adhesion, lymphangiogenesis, regulation of apoptosis, and so on. Some genes dedicating to the metastatic potential, including JAM2, TNC, CTSC, LAMB1, VEGFC, HAPLN1, ACPP, GDF9 and FGF11, were upregulated in LNMTca8113 cells. Conclusion: These results suggested that LNMTca8113 and Tca8113 cells were proper models for lymphatic metastasis study because there were differences in biologic behaviors and metastasis‐related genes between them. Additionally, the differentially expressed gene profiles in cancer progression may be helpful in exploring therapeutic targets and provide the foundation for further functional validation of these specific candidate genes for OSCC.