基质金属蛋白酶-2与结直肠癌浸润和转移的相关性

基质金属蛋白酶(MMPs)是含有9种酶蛋白分子的家族,可以导致基质膜和细胞间质成分破坏与降解,在恶性肿瘤的侵袭与转移中发挥重要作用.近年来研究证明MMP-2在肿瘤的浸润和转移中起了关键作用[1].本研究拟探讨MMP-2与结直肠癌发生、发展、浸润和转移的关系.     

胃癌患者血清Ⅳ型胶原降解酶活性的研究

近来的研究表明恶性肿瘤在其向外浸润、转移的过程中需溶解细胞外基质,其中基质金属蛋白酶（ｍａｔｒｉｘｍｅｔａｌｏｐｒｏｔｅｉｎａｓｅ,ＭＭＰＳ）发挥了重要作用。基底膜Ⅳ型胶原是细胞外基质的重要成份,ＭＭＰＳ对Ⅳ型胶原的降解在肿瘤进展中至关重要。为此,...     

基质金属蛋白酶的生物学特性及其在肝癌浸润转移中的作用

基质金属蛋白酶(matrix metalloproteinases,MMPs)家族是一簇Zn2+依赖性蛋白酶[1],其主要功能是降解细胞外基质(extracellular matrix,ECM)成分,在生理及病理过程中发挥着重要作用,如胚胎发育、创伤修复、血管再生、结缔组织病、牙周病及肿瘤的浸润和转移过程等[2-6].近年来MMPs在各种恶性肿瘤的转移和浸润中的作用成为研究热点[7-11].我们就其生物学特性及在肝癌浸润转移中的作用作一综述.     

去整合素-金属蛋白酶家族与肿瘤的研究进展

ADAM又称去整合素-金属蛋白酶,含有去整合素和金属蛋白酶功能结构域,具有细胞黏附和蛋白水解酶的功能,在细胞外基质的降解、细胞-细胞的黏连、细胞-基质的黏连、细胞融合及信号转导等细胞活动中具有重要作用,参与体内多种实体肿瘤形成、侵袭和转移等病理过程,在肿瘤的靶向治疗研究中可能具有重要价值。     

非小细胞肺癌中MMP-9、TIMP-1表达与转移和预后的关系

恶性肿瘤的浸润和转移是一个多阶段、多步骤、多种成分参与的序贯连续过程 ,肿瘤组织对细胞外基质 (ｅｘｔｒａｃｅｌｌｕｌａｒｍａｔｒｉｘ,ＥＣＭ)的降解是肿瘤细胞能否形成转移的关键步骤。目前研究证实基质金属蛋白酶 (ｍａｔｒｉｘｍｅｔａｌｌｏｐｒｏｔｅｉｎａｓｅ ,ＭＭＰ)与金属蛋白酶组织型抑制因子 (ｔｉｓｓｕｅｉｎｈｉｂｉｔｏｒｏｆｍｅｔａｌｌｏｐｒｏｔｅｉｎａｓｅ ,ＴＩＭＰ)是参与和调控此过程的重要胶原酶系统[1] 。材料与方法　 65例非小细胞肺癌 (ＮＳＣＬＣ)组织蜡块来自中国医科大学附属第一医院 1989～ 1992年…     

金属蛋白酶组织抑制因子-1、-2在子宫内膜异位症中的表达

金属蛋白酶抑制因子(TIMPs)是体内基质金属蛋白酶(MMPs)的天然特异性组织抑制剂，通过抑制MMPs的活性及其产生，调控细胞外基质(ECM)的合成和降解，在妊娠分娩、伤口愈合、肿瘤浸润与转移等一系列生理病理过程中发挥重要作用。子宫内膜异位症(EMT)虽是一种良性妇科疾病，但却具有     

基质金属蛋白酶与急性肺损伤/急性呼吸窘迫综合征

基质金属蛋白酶,在体内可由多种基质细胞和炎症细胞产生,能降解基底膜和细胞外基质的多种蛋白成分,各种致病因子的刺激可引起其异常表达,在组织重构与修复、炎症反应、肿瘤侵袭和转移中发挥重要作用。     

基质金属蛋白酶与p53及核因子κB在肿瘤侵袭转移中的研究进展

基质金属蛋白酶在肿瘤侵袭转移中起着非常重要的作用.而基质金属蛋白酶的分泌与p53突变及核因子κB信号传导通路激活相关.因此综述基质金属蛋白酶与p53及核因子κB之间的关系,有利于寻找更多的靶点,以控制肿瘤发生、浸润、转移.     

基质金属蛋白酶-9表达与非小细胞肺癌侵袭和转移的关系

非小细胞肺癌( NSCLC)占肺癌80％以上,常常在病变后期才被诊断出,大部分已发生浸润、转移,预后极差.细胞外基质(ECM)降解是引起肺癌侵袭、转移发生的主要因素.基质金属蛋白酶(matrix metalloproteinases,MMP)是一大族对ECM成分有特异降解作用的蛋白酶,通过降解ECM在NSCLC浸润和转移中起重要作用.MMP-9在体内、外多种恶性肿瘤中呈过表达,且可特异性降解基底膜,已成为MMP家族在恶性肿瘤进展方面的研究热点.     

基质金属蛋白酶MMP-2与肺癌关系的研究进展

基质金属蛋白酶是一大组金属离子依赖的蛋白酶,它能障解细胞外基质中的各种蛋白成分,在恶性肿瘤的侵袭中具有重要作用,而基质金属蛋白酶的家族中,又以基质金属蛋白酶-2在肿瘤侵袭与转移中的作用最为突出,本文综述了有关基质金属蛋白酶-2与肺癌的相关研究进展．     

基质金属蛋白酶2表达与胃癌侵袭及转移的关系

基质金属蛋白酶2（MMP-2）在肿瘤细胞介导的细胞外基质降解中起关键作用。其过度表达与人类多种恶性肿瘤侵袭转移潜能及预后密切相关。MMP-2高度表达的胃癌,其侵袭性和转移性较强,恶性程度较高,患者的预后较差。本文就MMP-2和胃癌侵袭转移的相关性及其作用机制和影响因素作一综述。     

MMP/TIMP、VEGF与肺癌的浸润和转移

肺癌的浸润和转移与基质金属蛋白酶（matrixmetalloproteinase，MMP）及其抑制剂基质金属蛋白酶组织抑制剂（tissue inhibitor of metalloproteinase,TIMP）、血管内皮生长因子 （vascular endothelial growth factor, VEGF）等多因素密切相关，深入研究肺癌中MMP／TIMP及VEGF的表达与功能，揭示肺癌的浸润与转移的机制，可为评估肺癌的浸润、转移及预后提供重要的参考指标。     

Significance of lymphatic invasion and cancer invasion-related proteins on lymph node metastasis in gastric cancer

Background and Aims:  Cancer invasion and metastasis are critical events for patient prognosis; however, the most important step in the whole process of lymph node (LN) metastasis in gastric cancer remains obscure. In this study, the significance of cancer cell behaviors, such as cell detachment, stromal invasion and lymphatic invasion on regional LN metastasis in gastric cancer was investigated by comprehensive immunohistochemistry.
Methods:  A total of 210 cases with gastric cancer were selected. These consisted of 105 cases with regional LN metastasis (LN[+] group) and 105 cases without LN metastasis (LN[–] group). Both groups exhibited the same depth of invasion. Cancer tissues were subjected to immunohistochemistry with antibodies against claudin-3, claudin-4, β-catenin, matrix metalloproteinase (MMP)-1, and MMP-2, as well as endothelial markers of lymphatic vessel endothelial hyaluronan receptor-1 and von Willebrand factor for the objective discrimination between lymphatics and blood vessels. The expression of each protein as well as the histopathological parameters were compared between LN(+) and LN(−) groups.
Results:  Along with lymphatic invasion by cancer cells and gross tumor size, MMP-1 expression in cancer cells at the invasive front of the primary tumor was a significant, independent predictor of LN metastasis. The expression of claudins and β-catenin was associated with the histopathological type of cancer, but not with LN status.
Conclusion:  Among the cancer invasion-related proteins examined, MMP-1 plays a vital role in LN metastasis of gastric cancer. Tumor size, lymphatic invasion and MMP-1 expression level at the invasive front were the predictive factors of LN metastasis of gastric cancer.     

Mechanism of metastasis by membrane type 1-matrix metalloproteinase in hepatocellular carcinoma

AIM: To investigate the precise role of membrane type 1-matrix metalloproteinase (MT1-MMP) in hepatocellular carcinoma (HCC) metastasis. METHODS: Human HCC cells Hep3B with overexpression of MT1-MMP were established by stable transfection, and compared with control cells carrying the empty vector. Cells were examined in vivo for their differences in the metastatic ability of athymic nude mice, and analyzed in vitro for their differences in invasion ability by invasion chamber coated with Matrigel, adhesion towards collagen I and migration through culture chamber. Cell proliferation and apoptosis in adherent and suspension status were evaluated by MTT and flow cytometry analysis. RESULTS: We found that overexpression of MT1-MMP could increase intrahepatic metastasis in nude mice with orthotopic implantation of HCC cells (incidence of 100% [MT1-MMP transfectants] vs 40% [vector control transfectants],P<0.05). MT1-MMP could also enhance cell invasion through Matrigel (107.7 vs 39.3 cells/field, P<0.001), adhesion towards matrix (0.30 vs 0.12 absorbance unit at 540 nm, P<0.001), cell migration (89.3 vs 39.0 cells/field, P<0.001), and cell proliferation (24.3 vs 40.5 h/doubling, P<0.001). We also observed that MT1-MMP supported cell survival (71.4% vs 23.9%, P<0.001) with reduced apoptosis (43.7% vs 51.0%,P<0.05) in an attachment-free environment. CONCLUSION: MT1-MMP overexpression could enhance metastasis. In addition to its active role in matrix degradation during tumor invasion, MT1-MMP enhances tumor cell survival upon challenge of detachment, which is important during metastasis when cells enter the circulation.     

Mechanism of metastasis by membrane type 1-matrix metalloproteinase in hepatocellular carcinoma

AIM: To investigate the precise role of membrane type1-matrix metalloproteinase (MT1-MMP) in hepatocellular carcinoma (HCC) metastasis.METHODS: Human HCC cells Hep3B with overexpression of MT1-MMP were established by stable transfection, and compared with control cells carrying the empty vector.Cells were examined in vivo for their differences in the metastatic ability of athymic nude mice, and analyzed in vitro for their differences in invasion ability by invasion chamber coated with Matrigel, adhesion towards collagen I and migration through culture chamber. Cell proliferation and apoptosis in adherent and suspension status were evaluated by MTT and flow cytometry analysis.RESULTS: We found that overexpression of MT1-MMP could increase intrahepatic metastasis in nude mice with orthotopic implantation of HCC cells (incidence of 100%[MT1-MMP transfectants] vs 40% [vector control transfectants], P＜0.05). MT1-MMP could also enhance cell invasion through Matrigel (107.7 vs 39.3 cells/field,P＜0.001), adhesion towards matrix (0.30 vs 0.12absorbance unit at 540 nm, P＜0.001), cell migration(89.3 vs 39.0 cells/field, P＜0.001), and cell proliferation(24.3 vs 40.5 h/doubling, P＜0.001). We also observed that MT1-MMP supported cell survival (71.4% vs 23.9%,P＜0.001) with reduced apoptosis (43.7% vs51.0%, P＜0.05)in an attachment-free environment.CONCLUSION: MT1-MMP overexpression could enhance metastasis. In addition to its active role in matrix degradation during tumor invasion, MT1-MMP enhances tumor cell survival upon challenge of detachment, which is important during metastasis when cells enter the circulation.     

基质金属蛋白酶9与肺癌的侵袭和转移

基质金属蛋白酶9(matrix metalloproteinase-9,MMP-9)具有降解细胞外基质和促进血管生成的作用,在肿瘤的侵袭和转移中起着重要的作用.本文就MMP-9的基因、分子结构、调控及近年来在肺癌领域的临床研究进展几个方面进行综述.     

膜型基质金属蛋白酶-1与肝细胞癌侵袭转移性的关系

目的 探索膜型基质金属蛋白酶－１（ｍｅｍｂｒａｎｅ－ｔｙｐｅ１ｍａｔｒｉｘ ｍｅｔａｌｌｏｐｒｏｔｅｉｎａｓｅ,ＭＴ１－ＭＭＰ）与肝细胞癌（ＨＣＣ）侵袭转移性的关系及以ＭＴ１－ＭＭＰ来判断肝细胞癌侵袭转移性的可能性和方法。方法 通过ＲＴ－ＰＣＲ对正常肝、ＨＣＣ及其癌旁组织、癌栓组织,裸鼠人肝癌高、低转移模型中的ＭＴ１－ＭＭＰｍＲＮＡ进行半定量研究,并与ＨＣＣ侵龚转移的病理指标进行统计分析,结果 正     

中性粒细胞弹性蛋白酶及其抑制剂与肺癌关系的研究进展

肿瘤转移作为一系列复杂事件的结果,这一过程需要很多酶的参与.中性粒细胞弹性蛋白酶在肺癌侵袭和转移中发挥重要作用,在生理条件下,中性粒细胞弹性蛋白酶有很多特殊的作用底物,过量的中性粒细胞弹性蛋白酶可导致弹力蛋白的降解,还可导致细胞外基质的降解.肺癌组织中的中性粒细胞弹性蛋白酶的量不仅可作为肺癌预后的独立指标,而且在重度联合免疫缺陷小鼠的肺癌种植模型中,一种特殊的中性粒细胞弹性蛋白酶抑制剂ONO-5046完全抑制了肺癌细胞的生长.中性粒细胞弹性蛋白酶免疫抑制剂的应用有望成为阻止肺癌侵袭和转移的有效方法.     

Study on the expression of matrix metallo proteinase-2 mRNA in human gastric cancer

lNTRODUCTlONDuringtumorinvasionandmetastasis,malignantcellsinprimarysiteacquiretheabilityt0degradeextracellularmatrix(ECM)andpenetratetissuebarriers.Ainongthepr0teolyticenzymeswhichdegradeECM,matrixmetalloprotenase(MMP)isoneoftheimportantones.MMP-2(72kDatypelVcollagenase)isamember0ftheMMPsgenefamilywhichdegradesthemacromoleculesofconnectivetissueandECM,suchascollagen,proteoglycans,lamininandfibr0nectin.ThusMMP-2isbelievedtoplayanimp0rtantroleintumorinvasionandmetastasis.Severalimm…     

Membrane-type 1 matrix metalloproteinase mRNA expression in colorectal cancer

PURPOSE: Membrane-type matrix metalloproteinases are recently described proteolytic enzymes belonging to the matrix metalloproteinase family. Initial studies have indicated that membrane-type matrix metalloproteinases are involved in tumor invasion and metastasis. Membrane-type 1 matrix metalloproteinase is the first membrane-type matrix metalloproteinase to be described. The aim of this study was to investigate the expression of membrane-type 1 matrix metalloproteinase mRNA in colorectal cancer. METHODS: Samples were collected from surgical specimens of patients with colorectal adenocarcinoma and were immediately frozen in liquid nitrogen and stored at –80°C until processed. Both normal and cancer tissue was taken from each patient. TNM stage, tumor differentiation, mucin production, and vascular invasion were assessed. Northern blotting was used to quantify membrane-type 1 matrix metalloproteinase mRNA levels in the samples using a membrane-type 1 matrix metalloproteinase cDNA clone. X-ray film images were digitized and densitometry was used to quantify bands. All samples were normalized against 18S rRNA levels. Results are expressed as the ratio of cancer to normal tissue levels. Statistical analysis was performed using analysis of variance, withP<0.05 accepted as the level of significance. RESULTS: A total of 32 samples were prospectively analyzed. The correlation between TNM stage and increased expression of membrane-type 1 matrix metalloproteinase mRNA in cancer tissue over normal tissue is expressed in the mean ratio of cancer to normal tissue expression for Stages I through IV, respectively: 1.4 ± 0.2 (12 patients); 4.1 ± 2.6 (8 patients); 3.4 ± 3 (7 patients); and 4.5 ± 5 (5 patients). Stage I is significantly different from Stages II and IV (P<0.05). These preliminary results show an overall increasing trend in membrane-type 1 matrix metalloproteinase expression with increasing tumor stage. However, there was no correlation between membrane-type 1 matrix metalloproteinase expression and mucin production, degree of tumor differentiation, or vascular invasion. CONCLUSION: Preliminary results indicate that membrane-type 1 matrix metalloproteinase levels correlate with increasing tumor stage.Supported in part by a research grant from the David G. Jagelman memorial research fund.Read at the meeting of The American Society of Colon and Rectal Surgeons, San Antonio, Texas, May 2 to 7, 1998.