PTEN基因与肿瘤浸润转移

PTEN是最近克隆的肿瘤抑制基因,能多途径调控肿瘤浸润转移过程,抑制肿瘤浸润和转移.PTEN能稳定和增强肿瘤细胞间粘附,抑制肿瘤细胞迁移扩散和非锚定依赖性生长,以及诱导失巢凋亡,并可抑制细胞外基质降解和肿瘤血管生成等,从而抑制肿瘤浸润和转移.     

信号传导与转录激活因子3与肿瘤侵袭和转移

信号传导与转录激活因子3(STAT3)在各种癌组织中表达均明显增高,STAT3蛋白通过对下游基因的调节发挥抑制调亡、促进细胞增殖、增加肿瘤细胞侵袭力的作用.STAT3有可能成为肿瘤治疗中一个新的治疗靶位,阻断STAT3信号传导通路可能降低肿瘤细胞的侵袭和转移、抑制肿瘤细胞生长,可为肿瘤治疗提供新的思路.     

Matrix metalloproteinases in tumor invasion and metastasis

Extensive work on the mechanisms of tumor invasion and metastasis has identified matrix metalloproteinases (MMPs) as key players in the events that underlie tumor dissemination. Studies using natural and synthetic MMP inhibitors, as well as tumor cells transfected with cDNAs encoding the MMPs characterized thus far have provided compelling evidence that MMP activity can induce or enhance tumor survival, invasion and metastasis. Because of the ability of MMPs to degrade extracellular matrix (ECM) proteins, the principal mechanism whereby MMPs promote tumor development has been thought to be the proteolytic breakdown of tissue barriers to invasion and the associated facilitation of circulating tumor cell extravasation. However, recent evidence stemming from the use of novel experimental approaches indicates that MMPs do not play a major role in the process of extravasation itself. Rather, they appear to promote intravasation (the process of penetrating the circulation following invasion of blood vessels) and regulate the relationship between tumor cells and host tissue stroma subsequent to extravasation. In addition, the discoveries that a growing number of proteolytically active MMPs may localize to the cell surface in association with adhesion receptors, and that MMP substrates include latent cytokines and growth factors, provide a new conceptual framework for the mechanisms whereby MMPs influence tumor behavior.     

Hemostasis and tumor invasion. Therapeutic implications

Plasminogen activator activity (PAA) has been detected in various tumor cells or in their excretion products. In some cell systems PAA is a symptom of cell transformation, but its amount is questionably correlated with the invasiveness of the tumor cells. Procoagulant and aggregation activities on platelets, have been demonstrated in various tumor cells. There are weakly correlated with the metastatic potential of these cells. In vivo, the treatment of animals by modifiers of the hemostasis, or of the fibrinolysis systems provides contradictory results. Some reduction of metastatic diffusion and increase of life span have been noted with Warfarin. Clinical trials are scarce and their methodology is debatable. When conclusive, a lengthening of the life span has been observed, but not a reduction of the metastatic spread as metastases were still present.     

自噬与恶性肿瘤侵袭转移的相关性

 在恶性肿瘤侵袭转移的复杂生物学过程中,肿瘤细胞必须适应不同的生存压力。自噬作为一种受诸多基因及其表达产物精细调控的细胞内生理反应,不仅可被激活以适应代谢应激和微环境变化,还可能与肿瘤细胞的上皮 间质转化（EMT）、肿瘤炎症、抵抗失巢凋亡、维持细胞休眠等侵袭转移机制密切相关。      

肿瘤嗜神经侵袭和肿瘤微环境研究进展

肿瘤嗜神经侵袭易引起患者疼痛以及肿瘤的复发,越来越受到重视.肿瘤微环境与肿瘤嗜神经侵袭密切相关,微环境中有多种因子参与了肿瘤嗜神经侵袭,肿瘤嗜神经侵袭也会改变微环境.本文从二者的相互作用,作一综述.     

Collagenolytic mechanisms in tumor cell invasion

Summary Connective tissue stroma and basement membrane structures probably present natural barriers to the migration of tumor cells. It has therefore been proposed that collagenolytic enzymes are required to facilitate the spread and invasion of tumor cells into host tissues. The collagenases and cathepsin B-like enzymes are thought to be involved, but the cellular source of collagenolytic activity at the tumor: host interface or invasion zone' remains obscure in most cases. The invasion zone of different tumors is very variable with regard to the type and numbers of host or tumor cells, as well as the type of collagenous matrix, and few generalities can be made. The existence within a tumor of specialised subpopulations of cells which have different metastatic potential has been postulated. As a consequence it seems plausible that the phenotypic expression of highly invasive or metastatic tumor cells should include the potential for generating collagenolytic activity. Immunolocalisation studies have demonstrated the production of type I and type IV collagenases at sites of tumor invasion, but it does not appear to be a continuous process and only a small proportion of tumor and/or host cells elaborate enzyme at any one moment. Collagenase production is invariably microenvironmental in nature and it seems likely that local host:tumor cell interactions are important in modulating collagenolysis. Macrophages and mast cells have been shown to stimulate collagenase expression by tumor and stromal cells in vitro, and it is proposed that these cells may assume a contributory role for the induction of collagenolytic activity in vivo. The collagenolytic mechanisms that operate at micro-foci of host:tumor junctions probably depend upon the type of collagen, the cellular composition and the extracellular ionic conditions of each invasion site. Either tumor or host cells may elaborate enzymes, this being dependent upon the type and/or tissue location of the invasive tumor.     

Secondary leukemias in refractory germ cell tumor patients undergoing autologous stem-cell transplantation using high-dose etoposide.

PURPOSE: To quantify the risk of secondary leukemias in relapsed testicular cancer patients undergoing autologous stem-cell transplantation with high-dose etoposide. PATIENTS AND METHODS: Single institution, retrospective study of germ cell tumor patients who underwent autologous transplantation using high-dose etoposide from 1987 to 2001. RESULTS: One hundred thirteen patients received high-dose etoposide and carboplatin followed by autologous stem-cell transplantations for germ cell tumors. Follow-up ranged from 12 to 166 months (median, 51 months). Three patients (2.6%; 95% CI, 0.55% to 7.50%) subsequently developed leukemia at an average of 16 months post-autologous transplantation (range, 11 to 21 months). All three had received tandem transplantations and had been heavily pretreated, including at least one prior cycle of etoposide. Following autologous transplantation, all three patients exhibited refractory cytopenias before developing overt leukemia. All leukemias were of myeloid lineage. One patient developed an M2 with a t(8,21) chromosomal translocation; another, an M5 with a t(11,19); and one patient exhibited an unclassified leukemia with cytogenetic abnormalities resulting in monosomy for 7p and partial monosomy of 7q. Treatment of the leukemias involved allogeneic bone marrow transplantation. CONCLUSION: High-dose chemotherapy using high-dose etoposide as therapy for relapsed germ cell tumors was associated with a 2.6% risk of developing a secondary myeloid leukemia. This figure was not significantly different from the expected rate of secondary leukemias when patients receive additional cycles of standard-dose etoposide as salvage chemotherapy for germ cell tumors. Other factors, including the use of platinum agents, may also have a role in leukemogenesis in this patient population.     

埃兹蛋白相关信号通路与肿瘤侵袭转移

埃兹蛋白(Ezrin)是一种重要的膜-细胞骨架连接分子,在骨肉瘤、乳腺癌等常见的恶性肿瘤中异常表达,并与肿瘤侵袭转移和预后有关,其作用机制复杂,根据组织细胞类型不同,涉及黏附分子信号途径、Rho、Akt等多条肿瘤相关的信号途径.因此,研究埃兹蛋白相关的肿瘤信号转导对认识肿瘤的进展有重要意义,埃兹蛋白可能成为新的肿瘤治疗...     

RECK基因与肿瘤侵袭转移

RECK是最近发现的基质金属蛋白酶(MMP)抑制基因,在肿瘤组织中低表达,与肿瘤的侵袭转移能力密切相关.现主要综述RECK的结构、功能及其与肿瘤侵袭转移关系的研究进展.     

Coronin1c与肿瘤侵袭和转移相关性研究进展

目的 冠蛋白(Coronins)家族通过调控肌动蛋白生物网络,参与细胞运动等生物活动.本研究介绍Coronins的基本情况,重点探究家族成员Coronin 1c参与侵袭和转移的机制,总结其在肿瘤中的研究进展.方法 应用检索Pubmed及CNKI期刊全文数据库检索系统,以"Coronin,冠蛋白"等为关键词,检索2016-11以前的相关文献,共检索到英文文献362条,中文文献24条.纳入标准:(1)冠蛋白的结构,机制及临床作用等;(2)Coronin 1c的相关研究进展.剔除标准:(1)除Coronin 1c之外的其他冠蛋白的相关研究;(2)Coronin 1c非肿瘤的相关研究.符合纳入标准的中文文献12条,英文文献79条,根据剔除标准剔除中文文献12条,英文文献63条,最后纳入分析26篇文献.结果 Coronin 1c通过与Rac1和F-actin发生反应,作用于细胞骨架及其调节因子,调节细胞活动,从而影响肿瘤的侵袭和转移.结论 虽然Coronin 1c已在医学领域有了广泛研究,但其对肿瘤领域,尤其是肿瘤的侵袭和转移方面还存在很大的研究空间,需要进一步研究其临床相关性.     

miRNA control of tumor cell invasion and metastasis

MicroRNAs have emerged as a novel class of noncoding RNAs that regulate gene expression at the post‐translational level in almost every biological event. A large body of evidence indicates that microRNAs regulate the expression of different genes that play an important role in cancer cell invasion, migration and metastasis. In this review, we briefly describe the role of various miRNAs in invasion, migration and metastasis which are essential steps during cancer progression.     

Fly Src: the Yin and Yang of tumor invasion and tumor suppression

The non-receptor tyrosine kinase Src is inactivated by the C-terminal Src kinase Csk. In a recent paper in Developmental Cell, Vidal et al. show that loss of Drosophila Csk (dCsk) in a large field of cells results in cell proliferation and disorganization of tissue architecture. In contrast, local inactivation of dCsk in a small field of cells results in loss of cells that are adjacent to normal tissue. This loss occurs by basal migration and death by apoptosis. These findings may shed light on mechanisms that restrain tumor initiation.     

Tiam1基因与肿瘤侵袭转移

肿瘤侵袭诱导基因(Tiam1)能够在多种肿瘤细胞中高表达,而且对于肿瘤细胞的侵袭和转移及细胞的信号传导都有极其重要的作用.     

Acid-mediated tumor invasion: a multidisciplinary study

The acid-mediated tumor invasion hypothesis proposes altered glucose metabolism and increased glucose uptake, observed in the vast majority of clinical cancers by fluorodeoxyglucose-positron emission tomography, are critical for development of the invasive phenotype. In this model, increased acid production due to altered glucose metabolism serves as a key intermediate by producing H(+) flow along concentration gradients into adjacent normal tissue. This chronic exposure of peritumoral normal tissue to an acidic microenvironment produces toxicity by: (a) normal cell death caused by the collapse of the transmembrane H(+) gradient inducing necrosis or apoptosis and (b) extracellular matrix degradation through the release of cathepsin B and other proteolytic enzymes. Tumor cells evolve resistance to acid-induced toxicity during carcinogenesis, allowing them to survive and proliferate in low pH microenvironments. This permits them to invade the damaged adjacent normal tissue despite the acid gradients. Here, we describe theoretical and empirical evidence for acid-mediated invasion. In silico simulations using mathematical models provide testable predictions concerning the morphology and cellular and extracellular dynamics at the tumor-host interface. In vivo experiments confirm the presence of peritumoral acid gradients as well as cellular toxicity and extracellular matrix degradation in the normal tissue exposed to the acidic microenvironment. The acid-mediated tumor invasion model provides a simple mechanism linking altered glucose metabolism with the ability of tumor cells to form invasive cancers.     

Role of collagenases in tumor cell invasion

Summary Collagenases are a family of metalloproteinases which may play a role in facilitating tumor cell invasion of the extracellular matrix. Tumor cells traverse two types of extracellular matrix: basement membranes and interstitial stroma, at multiple stages of the metastatic process. The matrix is a dense meshwork of collagen, proteoglycans, elastin and glycoproteins. Normally the matrix does not contain open spaces large enough for cell movement. Therefore numerous investigators have postulated that collagenolytic proteases, secreted by tumor cells or associated host cells, breakdown the extracellular matrix during tumor cell invasion. A large number of animal and human tumors have been shown to contain collagenase at a higher level than corresponding benign tissues. Separate collagenolytic metalloproteinases have been identified which degrade specific types of collagen. A basement membrane collagenolytic protease was shown to be elevated in a series of metastatic murine tumor cells. Immunologic studies using antibodies specific for collagenase have demonstrated that in vivo, tumor cells can produce collagenase. Therefore identification of collagenase in cultured lines of tumor cells is not an artifact of in vitro cultivation. In some cases, tumor cells may induce host cells to produce collagenase. The best evidence to date that collagenases actually play a role in invasion is derived from experiments in which natural collagenase inhibitors block tumor cell invasion of extracellular matrix in vitro.     

Growth factor-induced cell motility in tumor invasion

Tumor progression to the invasive and metastatic states dramatically enhances the morbidity and mortality of cancer. Rational therapeutic interventions will only be possible when we understand the molecular mechanisms governing the cell behavior underlying this transformation. For invasion, a subpopulation of tumor cells must recognize the extracellular matrix barrier, modify the barrier, migrate through the barrier, and then proliferate in the adjacent but ectopic locale. Prevention of any one of these steps would prevent invasion, but determining the most sensitively dysregulated step should provide the most promising therapeutic index. In many invasive tumors, upregulation of active motility is stimulated by growth factor receptor signaling, the EGF receptor being the most frequently implicated. Two key downstream molecular switches, PLC γand m-calpain, are required for growth factor-induced motility but not basal, matrix-stimulated motility. Inhibition of either of these enzymes blocks in vitro and in vivo invasion of prostate, breast, and bladder carcinomas and glioblastomas. These represent novel and potentially selective targets for drug development. Future advances in the imaging of tumors in animals and ex vivo organ culture systems should provide additional new targets.