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排序方式: 共有1577条查询结果,搜索用时 31 毫秒
1.
Tianjiao Lyu Yahui Jiang Nan Jia Xiaoxia Che Qin Li Yinhua Yu Keqin Hua Robert C. Bast Jr Weiwei Feng 《International journal of cancer. Journal international du cancer》2020,146(6):1553-1567
Detachment of cancer cells from the primary tumor and formation of spheroids in ascites is required for implantation metastasis in epithelial ovarian cancer (EOC), but the underlying mechanism of this process has not been thoroughly elucidated. To mimic this process, ovarian cancer cells were grown in 3D and 2D culture. Hey and OVCA433 spheroids exhibited decreased cell proliferation and enhanced adhesion and invasion. SMYD3 expression was elevated in ovarian carcinoma spheroids in association with increased H3K4 methylation. Depletion of SMYD3 by transient siRNA, stable shRNA knockdown and the SMYD3 inhibitor BCI-121 all decreased spheroid invasion and adhesion. Gene expression arrays revealed downregulation of integrin family members. Inhibition assays confirmed that invasion and adhesion of spheroids are mediated by ITGB6 and ITGAM. SMYD3-deficient cells regained the ability to invade and adhere after forced overexpression of SMYD3, ITGB6 and ITGAM. However, this biological ability was not restored by forced overexpression of SMYD3 in ITGB6- and/or ITGAM-deficient cancer cells. SMYD3 and H3K4me3 binding at the ITGB6 and ITGAM promoters was increased in spheroids compared to that in monolayer cells, and the binding was decreased when SMYD3 expression was inhibited, consistent with the expression changes in integrins. SMYD3 expression and integrin-mediated adhesion were also activated in an intraperitoneal xenograft model and in EOC patient spheroids. In vivo, SMYD3 knockdown inhibited tumor metastasis and reduced ascites volume in both the intraperitoneal xenograft model and a PDX model. Overall, our results suggest that the SMYD3-H3K4me3-integrin pathway plays a crucial role in ovarian cancer metastasis to the peritoneal surface. 相似文献
2.
Takahiro Ando Hidenori Kage Yoko Matsumoto Koichi Zokumasu Takuma Yotsumoto Keita Maemura Yosuke Amano Kousuke Watanabe Jun Nakajima Takahide Nagase Daiya Takai 《Cancer science》2020,111(1):200-208
Integrins are transmembrane proteins that mediate cell adhesion to the extracellular matrix. Integrin α11 (ITGA11) is not expressed in normal alveolar epithelial cells and is a known receptor for collagen. While integrin α11β1 overexpression in the tumor stroma has been associated with tumor growth and metastatic potential of non–small cell lung cancer (NSCLC), little is known about the role of ITGA11 in tumor cells. Thus, we examined the RNA expression of ITGA11 by quantitative RT‐PCR in 80 samples collected from NSCLC patients who had undergone surgical resection and analyzed the clinical outcomes. We found that high expression of ITGA11 was associated with lower recurrence‐free survival in all NSCLC patients (P = 0.043) and in stage I NSCLC patients (P = 0.049). These results were consistent with in silico analyses of the Cancer Genome Atlas database. We also analyzed cell proliferation, migration and invasion capacity in lung cancer cell lines after overexpression of ITGA11. Overexpression of ITGA11 in lung cancer cell lines had little effect on cell proliferation but resulted in increased migration and invasion capacity. Our findings suggest that ITGA11 plays a significant role in cancer migration and invasion, leading to higher recurrence. ITGA11 expression may be a predictor of poor prognosis in patients with surgically resected NSCLC. 相似文献
3.
4.
Sabrina Benedetto Roberta Pulito Simonetta Geninatti Crich Guido Tarone Silvio Aime Lorenzo Silengo Jrg Hamm 《Magnetic resonance in medicine》2006,56(4):711-716
Targeted imaging requires site-specific accumulation of a contrast agent (CA), and the properties of that agent must be selected according to the abundance of the target to obtain a signal above the detection limit of the instrument. However, numerical estimates of receptors per cell are rarely found in the literature. Integrin receptors would be particularly promising targets because of their accessibility from the blood stream and expression on activated neovascular endothelial cells. We systematically estimated the number of integrin receptors of cell lines and primary cells by flow cytometry analysis. Since integrin receptors are heterodimeric molecules, and alpha(v) forms complexes with various beta subunits, the numbers of alpha(v) and beta(3) subunits are therefore dissimilar. The observed values are 3 . 10(3)-1.4 . 10(4)/cell for alpha(v), and 5.3 . 10(2)-1.1 . 10(4)/cell for beta(3). Despite the low number of exposed receptors, we show that up to single-cell MR visualization can be achieved with the use of iron oxide beads complexed with antibodies as CAs. 相似文献
5.
目的:观察整合素β1在自身免疫性心肌炎小鼠心肌的表达变化。方法:猪肌凝蛋白皮下注射免疫Balb/c小鼠,建立慢性自身免疫性心肌炎模型,于初次免疫后14、30和60d对心肌组织进行病理学检查,同时用激光共聚焦技术和间接免疫荧光法检测整合素β1在心肌的表达变化。结果:在初次免疫后14d,小鼠心脏有局部炎症出现,整合素β1在心脏血管周围的表达高于正常组(P<0.05);在第30天,小鼠心脏炎性浸润更加明显,整合素β1在心肌的表达增强,显著高于正常组(P<0.05);第60天,小鼠心脏炎症细胞减少,而纤维化则开始出现,整合素β1在心肌的表达最强(P<0.05),且排列紊乱。结论:整合素β1在自身免疫性心肌炎的发生及发展过程中起着不同重要作用,整合素β可能参与自身免疫反应及心肌的重构。 相似文献
6.
For centuries snake venoms have been known to interfere with haemostasis and this is now known basically due either to toxins activating/inhibiting clotting factors, having effects on blood vessels or interfering with platelet function. In this short review, the interaction of one major group of toxins, the snake venom metalloproteinases, with platelets is considered. This is relevant for understanding the mechanism of haemorrhage induced by these toxins. 相似文献
7.
目的 :了解活化血小板葡萄糖摄取过程及血小板膜整合素对其影响 ,探讨整合素与血小板能量代谢的关系 ,旨在研究血小板能量代谢涉及的信号传导 ,并为目前临床应用血小板膜糖蛋白Ⅱb/Ⅲa(GPⅡb/Ⅲa)单抗抗血小板活化提供新的理论依据。方法 :用液态闪烁计数方法检测在血小板膜糖蛋白Ⅱb/Ⅲa单抗 10E5及血小板整合素αυβ3 单抗 6 0 9干预与否情况下凝血酶激活后血小板摄取氚标 2 脱氧葡萄糖 ([3 H]2 DG)率。结果 :在生理浓度范围内活化血小板 [3 H]2 DG摄取率较静息时明显升高 ,单抗 10E5可充分阻断活化血小板葡萄糖摄取 ,单抗 6 0 9可部分阻断。结论 :整合素家族单抗可抑制血小板激活后葡萄糖摄取 ,提示其可能参与血小板能量代谢信号传导过程 ,并可能以GPⅡb/Ⅲa为主 相似文献
8.
Michael Schirner Frank Herzberg Roland Schmidt Michael Streit Michael Schoning Michael Hummel Christine Kaufmann Eckhard Thiel Ernst-Dieter Kreuser 《Clinical & experimental metastasis》1997,16(5):427-435
The integrin 51 seems to be the most relevant receptor of tumor cells for binding to fibronectin. Although numerous studies suggest a role of tumor cell fibronectin interaction in tumor metastasis, differential integrin expression on tumor cells has, however, not been correlated with metastatic capabilities. We addressed this question by transfection of the integrin 51 cDNA into HT-29 human colon carcinoma cells which led to de novo expression of functional integrin 51. Similar to other reports, expression of the integrin 51 in HT-29 tumor cells exerted an inhibitory action on cell proliferation as indicated in our study by formation of fewer colonies in soft agar. The tumor growth inhibitory property of the integrin 51 was also shown by reduction of subcutaneous xenograft growth in nude mice to approximately 50% of that of control transfectants. For the first time, we found that several clones of integrin 5 subunit transfectants displayed dramatically reduced formation of lung colonies and cutaneous metastasis after intravenous injec-tion into nude mice. While most animals inoculated with control transfectant cells formed macroscopically visible lung colonies ranging from 12.6 ± 2.6 to 22.0 ± 6.6 (mean colony number ± SEM), mice inoculated with HT-29 cell clones expressing the integrin a5b1 were almost completely free of lung colonies (ranging from 0.0 ± 0 to 0.2 ± 0.1). Our results imply that integrin 51 expression inhibits circulating tumor cells in pursuing late steps of the metastatic process as represented by the artificial metastasis (lung colonisation) model. © Rapid Science Ltd. 相似文献
9.
Guanine nucleotide exchange factors of the cytohesin family and their roles in signal transduction 总被引:2,自引:0,他引:2
Waldemar Kolanus 《Immunological reviews》2007,218(1):102-113
Summary: Members of the cytohesin protein family, a group of guanine nucleotide exchange factors for adenosine diphosphate ribosylation factor (ARF) guanosine triphosphatases, have recently emerged as important regulators of signal transduction in vertebrate and invertebrate biology. These proteins share a modular domain structure, comprising carboxy-terminal membrane recruitment elements, a Sec7 homology effector domain, and an amino-terminal coiled-coil domain that serve as a platform for their integration into larger signaling complexes. Although these proteins have a highly similar overall build, their individual biological functions appear to be at least partly specific. Cytohesin-1 had been identified as a regulator of β2 integrin inside-out regulation in immune cells and was subsequently shown to be involved in mitogen-associated protein kinase signaling in tumor cell proliferation as well as in T-helper cell activation and differentiation. Cytohesin-3, which had been discovered to be strongly associated with T-cell anergy, was very recently described as an essential component of insulin signal transduction in Drosophila and in human and murine liver cells. Future work will aim to dissect the mechanistic details of the modes of action of the cytohesins as well as to define the precise roles of these versatile proteins in vertebrates at the genetic level. 相似文献
10.
Y.?Takeda N.?Shiobara A.?R.?Saniabadi M.?Adachi K.?HiraishiEmail author 《Inflammation research》2004,53(7):277-283
Objective:Evolving evidence of anti-inflammatory effects is observed in patients with rheumatoid arthritis or ulcerative colitis following periodic adsorptive granulocyte and monocyte (GM) apheresis with a column containing cellulose acetate (CA) beads as apheresis carriers. This study was undertaken to obtain insights into mechanisms of anti-inflammatory actions of adsorptive GM apheresis with CA beads.
Methods:In a series of in-vitro experiments, we investigated the effects of plasma proteins and the leucocytes 2 integrin (CD18) on granulocyte adsorption to CA beads.
Results:Granulocyte adsorption to CA beads required plasma IgG, the complement C3 and was inhibited by an antibody to leucocytes CD18. Further, hepatocyte growth factor (HGF) and interleukin-1 receptor antagonist (IL-1ra) which have strong anti-inflammatory actions were released by granulocytes that adhered to CA beads.
Conclusions:Plasma IgG, C3 derived complement activation fragments and leucocytes CD18 are involved in granulocyte adhesion to CA beads and hence the release of HGF and IL-1ra.Received 27 October 2003; returned for revision 16 December 2003; accepted by M. J. Parnham 8 January 2004 相似文献