Invasion & metastasis最新文献_第5页

Emerging roles for proteinases in cancer. 蛋白酶在癌症中的新作用。

Invasion & metastasis Pub Date : 1997-01-01

A Noël, C Gilles, K Bajou, L Devy, F Kebers, J M Lewalle, E Maquoi, C Munaut, A Remacle, J M Foidart

引用次数: 0

Use of tetracycline as an inhibitor of matrix metalloproteinase activity secreted by human bone-metastasizing cancer cells. 四环素作为人骨转移癌细胞分泌基质金属蛋白酶活性抑制剂的应用。

Invasion & metastasis Pub Date : 1997-01-01

W C Duivenvoorden, H W Hirte, G Singh

{"title":"Use of tetracycline as an inhibitor of matrix metalloproteinase activity secreted by human bone-metastasizing cancer cells.","authors":"W C Duivenvoorden, H W Hirte, G Singh","doi":"","DOIUrl":"","url":null,"abstract":"Bone metastases are a common complication in prostate and breast cancer patients. It leads to extensive morbidity and eventually mortality. Matrix metalloproteinases are implicated in various steps of development of metastasis, through their ability to degrade the extracellular matrix. Increased matrix metalloproteinase activity of tumor cells has been associated with a higher metastatic potential. Inhibitors of metalloproteinases have been shown to effectively reduce or prevent the formation of metastases. The family of tetracyclines is able to inhibit matrix metalloproteinase activity through chelation of the zinc ion at the active site of the enzyme. Using tumor cell lines relevant to bone metastases, i.e. PC-3, MDA-MB-231, Hs696, B16/F1, we showed that tetracycline and derivatives of tetracycline, namely doxycycline and minocycline, also induced cytotoxicity. The effective concentrations are relatively high for plasma, but are clinically achievable in the bone, since tetracyclines are osteotropic. All four bone-metastasizing tumor cells produced and secreted various matrix metalloproteinases. Doxycycline was able to inhibit the activity of 72- and 92-kDa type IV collagenase secreted by bone-metastasizing cells by 79-87%. These characteristics could make tetracycline a unique candidate as a therapeutic agent to prevent bone metastases in cancer patients with a high likelihood for development of bone metastasis. Studies using animal models of experimental bone metastasis will be necessary to confirm this.","PeriodicalId":14452,"journal":{"name":"Invasion & metastasis","volume":"17 6","pages":"312-22"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20854419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IL-10 inhibition of human prostate PC-3 ML cell metastases in SCID mice: IL-10 stimulation of TIMP-1 and inhibition of MMP-2/MMP-9 expression. IL-10对SCID小鼠人前列腺PC-3 ML细胞转移的抑制作用:IL-10刺激TIMP-1和抑制MMP-2/MMP-9的表达。

Invasion & metastasis Pub Date : 1997-01-01

M E Stearns, K Fudge, F Garcia, M Wang

{"title":"IL-10 inhibition of human prostate PC-3 ML cell metastases in SCID mice: IL-10 stimulation of TIMP-1 and inhibition of MMP-2/MMP-9 expression.","authors":"M E Stearns, K Fudge, F Garcia, M Wang","doi":"","DOIUrl":"","url":null,"abstract":"The molecular mechanism by which IL-10 inhibits metastases was examined using a SCID mouse model. Human PC-3 ML subclones normally metastasize to the lumbar vertebrae (approximately 70% mice injected, n = 14/20) following intravenous injection in severe combined immunodeficient (SCID) mice. IL-10 treatment of the PC-3 ML cells (15 ng/ml for 36 h) and the SCID mice (0.03 mg/kg/day for 30 days) reduced the number of metastases to 5% of the mice (n = 1/20). More importantly, following discontinuation of IL-10 treatment on day 30, the mice remained tumor-free and mouse survival rates increased dramatically (from < 30% in untreated mice) to about 85% in IL-10-treated mice. IL-10 did not appear to alter the growth rates or colony-forming ability of the PC-3 ML cells in vitro. Likewise, the growth of subcutaneous tumors and established bone marrow metastases was not inhibited by IL-10 treatment of the SCID mice. However IL-10 may inhibit the production of matrix metalloproteases (MMP) and prevent the establishment of metastasis. We therefore examined the influence of IL-10 on PC-3 ML production of MMP-2/MMP-9 and the tissue inhibitors of metalloproteinases (TIMP-1/2). Enzyme-linked immunosandwich assays (ELISAs) revealed that IL-10 (15 ng/ml for 36 h) treatment of the PC-3 ML cells down-regulated MMP-2 and MMP-9 while up-regulating TIMP-1 (not TIMP-2) expression. Likewise, IL-10-treated mice exhibited similar changes in TIMP-1 and MMP-2/MMP-9 expression. The IL-10 effects were blocked by IL-10 receptor antibodies. In comparison to IL-10, IL-4 failed to influence metastasis or the expression of TIMP-1, TIMP-2, MMP-2 and MMP-9 by PC-3 ML cells. We suggest that IL-10-regulated increases in the molar ratio of TIMP-1/MMP-9 and TIMP-2/MMP-2 might inhibit processes critical to the establishment of bone marrow metastasis.","PeriodicalId":14452,"journal":{"name":"Invasion & metastasis","volume":"17 2","pages":"62-74"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20481384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synergism of tumor necrosis factor-alpha and melphalan in systemic and regional administration: animal study. 肿瘤坏死因子- α和美法兰在全身和局部给药中的协同作用:动物研究。

Invasion & metastasis Pub Date : 1997-01-01

M Gutman, D Sofer, D Lev-Chelouche, O Merimsky, J M Klausner

{"title":"Synergism of tumor necrosis factor-alpha and melphalan in systemic and regional administration: animal study.","authors":"M Gutman, D Sofer, D Lev-Chelouche, O Merimsky, J M Klausner","doi":"","DOIUrl":"","url":null,"abstract":"Tumor necrosis factor (TNF) is a highly cytotoxic cytokine. However, due to its severe side effects, the only clinical situation allowing its administration in humans is isolated limb perfusion (ILP). Early studies have shown that TNF alone is of limited efficacy even at high doses via ILP, and that a chemotherapeutic agent needs to be added. The most commonly used drug in this setting is melphalan which is considered to be synergistic with TNF. However, since melphalan has not been commonly used in sarcoma, we believed that confirmation of its synergistic effect with TNF in an experimental sarcoma model could prove valuable for future drug choice. B16F10 melanoma and CT26 colon carcinoma cells were injected subcutaneously (s.c.) into mice, while GF fibrosarcoma cells were injected s.c. into the hindleg of Wistar rats. The animals were then divided into four treatment groups: TNF alone, melphalan alone, TNF and melphalan, and 0.9% NaCl controls. Mice were treated with intraperitoneal injections and rats by ILP. TNF dosage was 20 microgram for mice and 200 microgram for rats. Melphalan was given at 5-10 mg/kg for both mice and rats. Results showed synergism of TNF and melphalan in both modes of therapy. In the systemic administration groups (mice carrying B16F10 and CT26 tumors), tumors increased in size in all but the combined TNF-melphalan group. In the regional delivery groups (rats carrying GF sarcoma cells treated via ILP), there was a 16% decrease in tumor volume in rats treated with TNF alone, a 29% decrease in rats treated with melphalan, and a 75% decrease in the combined TNF-melphalan group. In conclusion, TNF and melphalan proved to be highly synergistic in both systemic and regional delivery. This fact makes melphalan an adequate choice for TNF perfusion in advanced limb malignancies.","PeriodicalId":14452,"journal":{"name":"Invasion & metastasis","volume":"17 4","pages":"169-75"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20691210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The small heat shock protein hsp27 increases invasiveness but decreases motility of breast cancer cells. 小的热休克蛋白hsp27增加了乳腺癌细胞的侵袭性，但降低了活动性。

Invasion & metastasis Pub Date : 1997-01-01

P Lemieux, S Oesterreich, J A Lawrence, P S Steeg, S G Hilsenbeck, J M Harvey, S A Fuqua

{"title":"The small heat shock protein hsp27 increases invasiveness but decreases motility of breast cancer cells.","authors":"P Lemieux, S Oesterreich, J A Lawrence, P S Steeg, S G Hilsenbeck, J M Harvey, S A Fuqua","doi":"","DOIUrl":"","url":null,"abstract":"The small heat shock protein hsp27 is often expressed at high levels in clinical breast tumors; however, its biological role in this disease still remains unclear. Several laboratories have recently shown that hsp27 expression is associated with aggressive tumor behavior. We hypothesized that hsp27 may influence the metastatic tumor process since this is part of tumor 'aggressiveness'. Therefore, we stably transfected breast cancer cell lines with sense (MDA-MB-231) and antisense (MDA-MB-435) hsp27 constructs, respectively, and examined various cellular aspects associated with the metastatic process. We found that hsp27-overexpressing clones lost their protrusive morphology, but exhibited higher membrane ruffling as compared to low expressing cells. hsp27 overexpression also resulted in decreased cell motility, but invasiveness, adhesion, and growth in Matrigel were all significantly increased. Conversely, antisense suppression of hsp27 expression resulted in increased cell motility, but decreased in vitro invasiveness. The direct correlation of hsp27 levels with metastasis was confirmed by an in vivo assay measuring the number of lung metastases in mice injected with hsp27-transfected cells. Thus, we conclude that hsp27 overexpression may influence the invasive and metastatic potential of human breast cancer cells.","PeriodicalId":14452,"journal":{"name":"Invasion & metastasis","volume":"17 3","pages":"113-23"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20619130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Increased type IV collagen-degrading activity in metastases originating from primary tumors of the human colon. 人结肠原发肿瘤转移灶中IV型胶原降解活性增高。

Invasion & metastasis Pub Date : 1997-01-01

G Karakiulakis, C Papanikolaou, S M Jankovic, A Aletras, E Papakonstantinou, E Vretou, V Mirtsou-Fidani

引用次数: 0

Spontaneous metastasis of rat liver epithelial cells transformed with v-raf and v-raf/v-myc: association with different phenotypic properties. v-raf和v-raf/v-myc转化大鼠肝上皮细胞的自发转移:与不同表型特性的关联

Invasion & metastasis Pub Date : 1997-01-01

H C Bisgaard, A R Mackay, D E Gomez, P T Ton, S S Thorgeirsson, U P Thorgeirsson

{"title":"Spontaneous metastasis of rat liver epithelial cells transformed with v-raf and v-raf/v-myc: association with different phenotypic properties.","authors":"H C Bisgaard, A R Mackay, D E Gomez, P T Ton, S S Thorgeirsson, U P Thorgeirsson","doi":"","DOIUrl":"","url":null,"abstract":"Cloned v-raf, v-raf/v-myc, and spontaneously transformed rat liver epithelial (RLE) cell lines were examined for meastatic capability in nude mice, using the LacZ gene as a marker for quantitation of micrometastases. Six cloned lines (R3611-T lines) derived from nude mouse xenografts of the v-raf transformed R3611-3 cells displayed variable metastatic capabilities. Three of six subcutaneously inoculated R3611-TlacZ lines produced spontaneous lung metastasis in nude mice. One of the lines, R3611-T2lacZ was highly efficient at metastatic conversion and produced more lung colonies than a faster growing v-raf/v-myc-transformed RJ2-14lacZ line. The spontaneously transformed RLElacZ line (C4T) was nonmetastatic, although it produced larger subcutaneous tumors than the metastatic R3611-T2lacZ line. Metastatic conversion correlated with upregulation of urokinase-type plasminogen activator receptor RNA expression and downregulation of plasminogen activator inhibitor-1, collagen alpha1 (I), and cytokeratin 14 (K14) RNA expression. These findings indicate that proteolytic activities associated with plasminogen activation play a role in the metastatic development in this model. Decreased production of extracellular proteins and cytoskeletal changes associated with lack of K14 expression are also likely to have contributed to the metastatic conversion of the RLE transformants.","PeriodicalId":14452,"journal":{"name":"Invasion & metastasis","volume":"17 5","pages":"240-50"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20784004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of bacterial association on the phenotype and genotype of an Entamoeba histolytica clonal population. 细菌关联对溶组织内阿米巴克隆群体表型和基因型的影响。

Invasion & metastasis Pub Date : 1997-01-01

L F De Menezes, M A Rodríguez, M A Vargas, L M Salgado, E Orozco

{"title":"Effect of bacterial association on the phenotype and genotype of an Entamoeba histolytica clonal population.","authors":"L F De Menezes, M A Rodríguez, M A Vargas, L M Salgado, E Orozco","doi":"","DOIUrl":"","url":null,"abstract":"A several-times-cloned population of Entamoeba histolytica trophozoites (clone MAVIII) was cultured under axenic (MAVIIIax), monoxenic (MAVIIImx) and polyxenic (MAVIIIpx) conditions. Clones MAVIIIax and MAVIIImx presented similar virulence in vitro, but differed in their virulence in vivo, whereas MAVIIIpx trophozoites were neither virulent in vitro or in vivo. The MAVIII clones maintained their zymodeme and exhibited three unusual glucose phosphate isomerase bands, absent in other E. histolytica strains studied. Similar patterns were shown by the three MAVIII clones in the signature of a 482-bp DNA fragment from the M17 gene (which encodes for a variable immunodominant antigen), obtained by low stringency single specific primer PCR technique. However, MAVIII clones displayed genotypic variability in the patterns obtained by the random amplified polymorphic DNA technique using total DNA as template. Results suggest that monomorphism is kept in certain regions of the genome, mainly in those carrying protein encoding genes, but a high polymorphism is present in total DNA of cloned trophozoites cultured under different conditions, confirming the plasticity of the E. histolytica genome.","PeriodicalId":14452,"journal":{"name":"Invasion & metastasis","volume":"17 4","pages":"176-88"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20691211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Endothelial cell response to human head and neck squamous cell carcinomas involves downregulation of protein phosphatases-1/2A, cytoskeletal depolymerization and increased motility. 内皮细胞对人头颈部鳞状细胞癌的反应包括蛋白磷酸酶-1/ 2a的下调、细胞骨架解聚和运动增加。

Invasion & metastasis Pub Date : 1997-01-01

J Benefield, J Meisinger, G J Petruzzelli, M R Young

引用次数: 0

Sequential steps in hematogenous metastasis of cancer cells studied by in vivo videomicroscopy. 活体视频显微镜研究癌细胞血行转移的顺序步骤。

Invasion & metastasis Pub Date : 1997-01-01

V L Morris, E E Schmidt, I C MacDonald, A C Groom, A F Chambers

{"title":"Sequential steps in hematogenous metastasis of cancer cells studied by in vivo videomicroscopy.","authors":"V L Morris, E E Schmidt, I C MacDonald, A C Groom, A F Chambers","doi":"","DOIUrl":"","url":null,"abstract":"Understanding metastatic spread of cancer is of upmost importance to developing successful strategies to treat this disease. In this review, we present a picture of the process of hematogenous metastasis from the initial arrest of cancer cells, their extravasation, postextravasation migration, and their replication to form tumors, based on experimental results using in vivo videomicroscopy. The cancer cells are initially arrested by size constraints within minutes of entering the circulation and with little hemodynamic destruction. Within 24-48 h >80% of these cancer cells extravasate as single cells by adhesion to and spreading along the vessel wall, often using pseudopodial projections to move into the surrounding tissue without disrupting the microcirculation. Some of the extravasated cells also use pseudopodial projections to migrate to specific structures in the tissue where they can replicate. Many cancer cells can persist as dormant cells, neither dividing nor undergoing apoptosis. Only a small fraction of extravasated cells begin to divide to form micrometastases, and only a very small fraction of these micrometastases continue to grow to form tumors. Possible clinical implications are that (1) initial arrest and extravasation may be difficult to prevent and thus may be poor therapeutic targets; (2) dormant single cells will not be affected by conventional cancer therapies which are designed to treat actively growing cells; and (3) regulation of growth of cells after extravasation is key to determining whether clinically evident metastases form - this stage of metastasis thus offers promising targets for new antimetastasis drugs.","PeriodicalId":14452,"journal":{"name":"Invasion & metastasis","volume":"17 6","pages":"281-96"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20854417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0