共查询到19条相似文献,搜索用时 171 毫秒
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陈量孙立袁胜涛 《现代生物医学进展》2011,11(21):4175-4177
肿瘤的微环境对肿瘤的发生,发展具有重要的意义。实体瘤中除肿瘤细胞外存在大量的非肿瘤细胞,如肿瘤间质细胞、成纤维细胞、血管内皮细胞、免疫细胞、脂肪细胞等等,这一系列的细胞与肿瘤细胞相互作用,通过一系列的因子分泌而促使肿瘤的进一步的恶化,目前传统的抗肿瘤药物研究往往局限于肿瘤细胞本身而忽略了肿瘤周围的细胞作用,使得肿瘤久治不愈。将来的药物开发应该围绕肿瘤细胞为主体的同时,兼顾微环境中的其他细胞,多靶点治疗肿瘤,真正实现肿瘤的治愈。 相似文献
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转化生长因子β(transforming growth factorβ,TGF-β)是一种多功能的细胞因子,能够调控细胞增殖、分化、黏附、迁移及凋亡等行为,在胚胎发育过程和成体组织稳态维持中发挥重要的作用。而在许多疾病状态下,特别是在癌症中,TGF-β不仅能够影响肿瘤细胞的增殖与转移,其对于肿瘤微环境的调控与塑造也受到越来越多的关注。肿瘤微环境是指肿瘤在发生和发展过程中所处的内环境,由肿瘤细胞本身、相邻正常组织中的间质细胞,以及这些细胞所释放的众多细胞因子等共同组成。肿瘤微环境是肿瘤发展的重要机制,也是肿瘤临床治疗领域亟待探索的关键问题。TGF-β是调节肿瘤微环境组成和功能的主要参与者之一。在本综述中,将着重讨论TGF-β对于肿瘤微环境中的免疫监视机制及肿瘤细胞外基质的主要影响。即TGF-β对于构成先天性和获得性抗肿瘤免疫应答的各种类群的免疫细胞具有广泛的调控作用,从而削弱宿主的肿瘤免疫监视功能。同时,TGF-β通过促进肿瘤相关成纤维细胞的产生,以及肿瘤细胞外基质的纤维化,有助于肿瘤的恶变和转移。此外,还介绍了通过阻断肿瘤微环境中TGF-β信号通路进行肿瘤治疗的主要策略及独特优势。而未来进一步解析TGF-β信号在肿瘤微环境中的复杂调控作用,并建立有效的靶向干预方法对于开发高效的抗肿瘤药物具有重要的意义。 相似文献
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研究表明,肿瘤转移是恶性肿瘤的临床治疗失败的根本原因。肿瘤转移不仅取决于肿瘤细胞自身的特性,还涉及其与肿瘤酸性微环境之间的相互作用。肿瘤微环境构成非常复杂,可促进肿瘤的增生、转移、侵袭,以及逃避宿主免疫监视和治疗耐药性。肿瘤细胞的生存依赖于在酸性微环境条件下的适应,肿瘤细胞可以通过一些离子交换体维持酸性微环境,缺氧的肿瘤组织酸化可以释放蛋白酶如纤维蛋白酶及MMPs降解细胞外基质、上调VEGF基因表达促进肿瘤新生血管生成等促进肿瘤侵袭转移。近年来,影响肿瘤微环境的因素已经成为癌症研究领域中的新兴话题。 相似文献
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肿瘤微环境(tumor microenvironment,TME)包含肿瘤组织中各种细胞如肿瘤细胞、免疫细胞、成纤维细胞等,还包含这些细胞分泌的各种可溶性因子,以及代谢底物(如葡萄糖)和代谢产物(如乳酸)等等。由于肿瘤细胞和免疫细胞对营养共同的大量需求,肿瘤微环境中的肿瘤细胞和T细胞之间会发生营养代谢竞争。这种微环境中的营养竞争已经被证明和抗肿瘤免疫抑制的发生密切相关,但同时这种关联也是复杂的和多因素的。肿瘤微环境中的共抑制分子的表达、葡萄糖的竞争、氨基酸的竞争、氧的竞争以及乳酸的分泌等等,共同成为了免疫抑制表型的重要促进因素。这些研究也给肿瘤的治疗提供了新的方向。本文从肿瘤细胞和T细胞代谢重编程出发,介绍不同的微环境因素对T细胞的影响。 相似文献
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除了依赖于肿瘤细胞自身的恶性增殖以外,肿瘤的发生和发展还依赖于肿瘤细胞与肿瘤间质微环境的相互作用。肿瘤间质中存在的肿瘤相关成纤维细胞(tumor-associatedfibroblasts,TAF)能够诱导免疫抑制,是肿瘤免疫治疗中的一大障碍。在TAF上存在一种成纤维细胞激活蛋白(fibroblast activationprotein,FAP),它在细胞表面发挥作用,是一种膜丝氨酸肽酶,是Ⅱ型丝氨酸蛋白酶家族成员之一,具有二肽肽酶及胶原酶活性,在肿瘤微环境中表达FAP的肿瘤相关成纤维细胞是最早被鉴定的一种肿瘤间质细胞类型。它由肿瘤问质中的成纤维细胞与癌细胞相互作用而活化,是肿瘤微环境中最主要的宿主细胞,具有促进肿瘤细胞生长、侵袭及免疫抑制的作用,而且基因组稳定不易耐药,有望成为肿瘤免疫治疗的新靶标。就靶向TAF和FAP在肿瘤免疫治疗中的研究做一综述,为基于肿瘤间质微环境的免疫治疗提供参考。 相似文献
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《中国生物化学与分子生物学报》2016,(10)
黏着斑激酶(focal adhesion kinase,FAK)是一种胞质非受体酪氨酸激酶。FAK和肿瘤密切相关,在多种癌细胞中高表达,促进癌细胞的发生、生长、存活、增殖、粘附、转移和侵袭以及血管生成等过程。肿瘤微环境包括肿瘤细胞、周围血管、免疫细胞、纤维母细胞、内皮细胞、信号分子和细胞外基质,它对癌症的发展和恶化具有重要作用。肿瘤细胞可以通过分泌细胞外信号影响微环境,使其有利于肿瘤生存和发展;肿瘤微环境中的基质细胞能通过产生趋化因子、基质降解酶和生长因子促进肿瘤侵袭和转移。本文综述肿瘤微环境在癌症发生发展过程中的作用及FAK在肿瘤微环境中的调控作用,为肿瘤疾病的治疗提供新思路。 相似文献
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Gretel Mendoza-Almanza Luis Burciaga-Hern ndez Vilma Maldonado Jorge Melendez-Zajgla Jorge Olmos 《World journal of stem cells》2020,12(11):1237-1254
The high mortality rate of breast cancer is mainly caused by the metastatic ability of cancer cells, resistance to chemotherapy and radiotherapy, and tumor regression capacity. In recent years, it has been shown that the presence of breast cancer stem cells is closely associated with the migration and metastatic ability of cancer cells, as well as with their resistance to chemotherapy and radiotherapy. The tumor microenvironment is one of the main molecular factors involved in cancer and metastatic processes development, in this sense it is interesting to study the role of platelets, one of the main communicator cells in the human body which are activated by the signals they receive from the microenvironment and can generate more than one response. Platelets can ingest and release RNA, proteins, cytokines and growth factors. After the platelets interact with the tumor microenvironment, they are called "tumor-educated platelets." Tumor-educated platelets transport material from the tumor microenvironment to sites adjacent to the tumor, thus helping to create microenvironments conducive for the development of primary and metastatic tumors. It has been observed that the clone capable of carrying out the metastatic process is a cancer cell with stem cell characteristics. Cancer stem cells go through a series of processes, including epithelial-mesenchymal transition, intravasation into blood vessels, movement through blood vessels, extravasation at the site of the establishment of a metastatic focus, and site colonization. Tumor-educated platelets support all these processes. 相似文献
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关于恶性肿瘤发生、复发与转移机制的研究由来已久,但目前的临床治疗方法依然不能克服肿瘤复发与转移的难题,肿瘤患者的生存率并未得到显著改善。近年来的研究提示肿瘤的起源、复发与转移的真正原因可能是存在于肿瘤内的极少数具有干细胞特性的细胞,即肿瘤干细胞(cancer stem cells,CSC)。与此同时,越来越多的研究表明,对于肿瘤干细胞的发生与功能维持,表观遗传学的调控机制可能发挥着极其重要的作用。该文简要综述目前肿瘤干细胞和表观遗传学相关领域的研究进展,并对肿瘤干细胞形成及发展过程中表观遗传学的调控作用及机制进行重点介绍。 相似文献
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Rengaswami Rajaraman Murali M. Rajaraman Selva R. Rajaraman Duane L. Guernsey 《Cell biology international》2005,29(12):1084
We recently described a novel form of cell division termed neosis, which appears to be the mode of escape of cells from senescence and is involved in the neoplastic transformation and progression of tumors (Cancer Biol & Therap 2004;3:207–18). Neosis is a parasexual somatic reduction division and is characterized by (1) DNA damage-induced senescence/mitotic crisis and polyploidization, (2) followed by production of aneuploid daughter cells via nuclear budding, (3) asymmetric cytokinesis and cellularization conferring extended, but, limited mitotic life span to the offspring, and (4) is repeated several times during tumor growth. The immediate neotic progeny are termed the Raju cells, which seem to transiently display stem cell properties. The Raju cells immediately undergo symmetric mitotic division and become mature tumor cells. Exposure of tumor cells to genotoxic agents yields neosis-derived Raju cell progenies that are resistant to genotoxins, thus contributing to the recurrence of drug-resistant tumor growth. Similar events have been described in the literature under different names through several decades, but have been neglected due to the lack of appreciation of the significance of this process in cancer biology. Here we review and interpret the literature in the light of our observations and the recent advances in self-renewal in cancer. Neosis paradigm of self-renewal of cancer growth is consistent with the telomere attrition, aging and origin of cancer cells after reactivation of telomerase, and constitutes an alternative to the cancer stem cell hypothesis. We summarize the arguments favoring Raju cells and not cancer stem cells, as the source of self-renewal in cancer and present a comprehensive hypothesis of carcinogenesis, encompassing various aspects of cancer biology including senescence, tumor suppressor genes, oncogenes, cell cycle checkpoints, genomic instability, polyploidy and aneuploidy, natural selection, apoptosis, endoapoptosis, development of resistance to radiotherapy and chemotherapy leading tumor progression into malignancy. 相似文献
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Neosis--a paradigm of self-renewal in cancer 总被引:3,自引:0,他引:3
We recently described a novel form of cell division termed neosis, which appears to be the mode of escape of cells from senescence and is involved in the neoplastic transformation and progression of tumors (Cancer Biol & Therap 2004;3:207-18). Neosis is a parasexual somatic reduction division and is characterized by (1) DNA damage-induced senescence/mitotic crisis and polyploidization, (2) followed by production of aneuploid daughter cells via nuclear budding, (3) asymmetric cytokinesis and cellularization conferring extended, but, limited mitotic life span to the offspring, and (4) is repeated several times during tumor growth. The immediate neotic progeny are termed the Raju cells, which seem to transiently display stem cell properties. The Raju cells immediately undergo symmetric mitotic division and become mature tumor cells. Exposure of tumor cells to genotoxic agents yields neosis-derived Raju cell progenies that are resistant to genotoxins, thus contributing to the recurrence of drug-resistant tumor growth. Similar events have been described in the literature under different names through several decades, but have been neglected due to the lack of appreciation of the significance of this process in cancer biology. Here we review and interpret the literature in the light of our observations and the recent advances in self-renewal in cancer. Neosis paradigm of self-renewal of cancer growth is consistent with the telomere attrition, aging and origin of cancer cells after reactivation of telomerase, and constitutes an alternative to the cancer stem cell hypothesis. We summarize the arguments favoring Raju cells and not cancer stem cells, as the source of self-renewal in cancer and present a comprehensive hypothesis of carcinogenesis, encompassing various aspects of cancer biology including senescence, tumor suppressor genes, oncogenes, cell cycle checkpoints, genomic instability, polyploidy and aneuploidy, natural selection, apoptosis, endoapoptosis, development of resistance to radiotherapy and chemotherapy leading tumor progression into malignancy. 相似文献
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Josiane W. Tessmann Murilo R. Rocha Jose A. Morgado-Díaz 《Journal of cellular biochemistry》2023,124(1):31-45
Radiotherapy is one of the most common modalities for the treatment of a wide range of tumors, including colorectal cancer (CRC); however, radioresistance of cancer cells remains a major limitation for this treatment. Following radiotherapy, the activities of various cellular mechanisms and cell signaling pathways are altered, resulting in the development of radioresistance, which leads to therapeutic failure and poor prognosis in patients with cancer. Furthermore, even though several inhibitors have been developed to target tumor resistance, these molecules can induce side effects in nontumor cells due to low specificity and efficiency. However, the role of these mechanisms in CRC has not been extensively studied. This review discusses recent studies regarding the relationship between radioresistance and the alterations in a series of cellular mechanisms and cell signaling pathways that lead to therapeutic failure and tumor recurrence. Our review also presents recent advances in the in vitro/in vivo study models aimed at investigating the radioresistance mechanism in CRC. Furthermore, it provides a relevant biochemical basis in theory, which can be useful to improve radiotherapy sensitivity and prolong patient survival. 相似文献
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Tomasz Kolenda Weronika Przybyła Marta Kapałczyńska Anna Teresiak Maria Zajączkowska Renata Bliźniak Katarzyna M. Lamperska 《Reports of Practical Oncology and Radiotherapy》2018,23(3):143-153
Head and neck squamous cell carcinomas (HNSCC) are in a group of cancers that are the most resistant to treatment. The survival rate of HNSCC patients has been still very low since last 20 years. The existence of relationship between oncogenic and surrounding cells is probably the reason for a poor response to treatment. Fibroblasts are an important element of tumor stroma which increases tumor cells ability to proliferate. Another highly resistance, tumorigenic and metastatic cell population in tumor microenvironment are cancer initiating cells (CICs). The population of cancer initiating cells can be found regardless of differentiation status of cancer and they seem to be crucial for HNSCC development.In this review, we describe the current state of knowledge about HNSCC biological and physiological tumor microenvironment. 相似文献
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Postovit LM Costa FF Bischof JM Seftor EA Wen B Seftor RE Feinberg AP Soares MB Hendrix MJ 《Journal of cellular biochemistry》2007,101(4):908-917
Aggressive cancer cells and pluripotent stem cells converge in their capacity for self-renewal, proliferation and plasticity. Recent studies have capitalized on these similarities by demonstrating that tumors arise from specific cancer stem cell populations that, in a manner reminiscent of normal stem cells, are able to both self-renew and give rise to a heterogeneous tumor population. This stem cell like function of aggressive cancer cells is likely attributable to the ectopic expression of embryonic factors such as Nodal and Cancer Testis Specific Antigens (CTAs), which maintain a functional plasticity by promoting pluripotency and immortality. During development, the expression of these embryonic factors is tightly regulated by a dynamic array of mediators, including the spatial and temporal expression of inhibitors such as Lefty, and the epigenetic modulation of the genome. In aggressive cancer cells, particularly melanoma, this balance of regulatory mediators is disrupted, leading to the aberrant expression of pluripotency-associated genes. By exposing aggressive cancer cells to embryonic microenvironments, this balance of regulatory mediators is restored, thereby reprogramming tumor cells to a more benign phenotype. These stem cell-derived mediators, as well as the genes they regulate, provide therapeutic targets designed to specifically differentiate and eradicate aggressive cancers. 相似文献
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《Expert review of proteomics》2013,10(6):579-589
Metastasis is the main cause of cancer death. As the tumor progresses, cells from the primary tumor site are shed into the bloodstream as circulating tumor cells (CTCs). Eventually, these cells colonize other organs and form distant metastases. It is therefore imperative that we gain a better understanding of the biological characteristics of CTCs for development of novel treatment modalities to minimize metastasis-associated cancer deaths. In recent years, rapid developments in technologies for the study of CTCs have taken place. We now have a variety of tools for the isolation and examination of CTCs which were not available before. This review introduces some commonly used protein markers in CTC investigations and summarizes a few advanced technologies which have been successfully applied for studying CTC biology at the protein level. 相似文献