炎症介质与肿瘤血管生成

炎症介质不仅在肿瘤的发生发展过程中起到了重要的作用,在肿瘤的血管生成方面也扮演着重要的角色。炎症反应的调节通路和肿瘤血管生成调节通路存在较大的重叠。研究证实,包括COX-2、IL-1、IL-6等在内的众多炎症介质不仅能够促进肿瘤血管生成,在肿瘤血管拟态形成及肿瘤干细胞向血管内皮细胞定向分化过程中可能也起到积极的促进作用。     

肿瘤干细胞与肿瘤血管生成

肿瘤血管新生的过程是在一系列正反馈和负反馈因子作用下发生的复杂的链级反应.肿瘤干细胞是存在于肿瘤中一小部分具有自我更新和多向分化潜能的细胞群体.大量研究表明,肿瘤干细胞参与并促进肿瘤的血管新生,血管内皮生长因子能够调节内皮增殖和血管生成,从而促进肿瘤的生长和转移.     

Adipose-derived stem cells promote tumor initiation and accelerate tumor growth by interleukin-6 production

Adipose-derived stem cells (ADSCs) are multipotent cells that have attracted much recent attention. Here, we show that ADSCs enhance sphere formation and in vivo tumor initiation of breast and colon cancer cells. In co-culture, ADSCs induced several stem cell markers in cancer cells. ADSCs also accelerated tumor growth. Interaction of ADSCs and cancer cells stimulated secretion of interlukin-6 in ADSCs, which in turn acted in a paracrine manner on cancer cells to enhance their malignant properties. Interleukin-6 regulated stem cell-related genes and activated JAK2/STAT3 in cancer cells. We suggest that ADSCs may enhance tumor initiation and promotion.     

Chemokines in tumor angiogenesis and metastasis

Chemokines are a large group of low molecular weight cytokines that are known to selectively attract and activate different cell types. Although the primary function of chemokines is well recognized as leukocyte attractants, recent evidences indicate that they also play a role in number of tumor-related processes, such as growth, angiogenesis and metastasis. Chemokines activate cells through cell surface seven trans-membranes, G-protein-coupled receptors (GPCR). The role played by chemokines and their receptors in tumor pathophysiology is complex as some chemokines favor tumor growth and metastasis, while others may enhance anti-tumor immunity. These diverse functions of chemokines establish them as key mediators between the tumor cells and their microenvironment and play critical role in tumor progression and metastasis. In this review, we present some of the recent advances in chemokine research with special emphasis on its role in tumor angiogenesis and metastasis.     

肿瘤干细胞的来源

肿瘤干细胞是肿瘤演化的单位,阐明肿瘤干细胞的来源对于肿瘤的防治有重要意义.综合近年相关文献和工作中的体会探讨肿瘤干细胞的可能来源、产生途径和机制.正常干细胞转化为肿瘤干细胞需要经历漫长的基因突变积累过程;诱导重编程形成多潜能干细胞是体细胞产生肿瘤干细胞的可能途径之一;肿瘤细胞返分化为肿瘤干细胞是肿瘤干细胞来源之一;上皮-间充质转换(EMT)是细胞可塑性的重要机制,在肿瘤细胞转移和肿瘤细胞干性形成中起重要作用,细胞融合诱导EMT可能是肿瘤干细胞形成的另一重要机制;此外,一些病毒感染可能与肿瘤干细胞形成相关.文章对肿瘤生物学性状复杂性的机制也进行了讨论.     

Aquaporins in tumor growth and angiogenesis

The aquaporins (AQPs) are a family of transmembrane water channel proteins widely distributed and play a major role in transcellular and transepithelial water movement. Moreover, recent evidence indicates that AQPs may be involved in cell migration and angiogenesis. This review article summarizes literature data concerning the involvement of AQPs in tumor growth, angiogenesis and metastatic process and suggest a potential therapeutic approach by antagonizing their biological activity.     

Brain tumor stem cells: The cancer stem cell hypothesis writ large

Brain tumors, which are typically very heterogeneous at the cellular level, appear to have a stem cell foundation. Recently, investigations from multiple groups have found that human as well as experimental mouse brain tumors contain subpopulations of cells that functionally behave as tumor stem cells, driving tumor growth and generating tumor cell progeny that form the tumor bulk, but which then lose tumorigenic ability. In human glioblastomas, these tumor stem cells express neural precursor markers and are capable of differentiating into tumor cells that express more mature neural lineage markers. In addition, modeling brain tumors in mice suggests that neural precursor cells more readily give rise to full blown tumors, narrowing potential cells of origin to those rarer brain cells that have a proliferative potential. Applying stem cell concepts and methodologies is giving fresh insight into brain tumor biology, cell of origin and mechanisms of growth, and is offering new opportunities for development of more effective treatments. The field of brain tumor stem cells remains very young and there is much to be learned before these new insights are translated into new patient treatments.     

Brain tumor stem cells as research and treatment targets

Glioblastoma multiforme (GBM) is one of the most malignant forms of human cancer. Despite intensive treatment, the mean survival of GBM patients remains about 1 year. Recent cancer studies revealed that cancer tissues are pathologically heterogeneous and only a small population of cells has the specific ability to reinitiate cancer. This small cell population is called cancer stem cells (CSCs); in brain tumors these are known as brain tumor stem cells (BTSCs). The identification of BTSCs yielded new insights into chemo-and radioresistance, by which BTSCs can survive selectively and initiate recurrence. Research focused on BTSCs as treatment targets may contribute to the discovery of new therapeutic strategies.     

肿瘤相关巨噬细胞与肿瘤关系的研究进展

肿瘤相关巨噬细胞（ Tumor associate macrophages ,TAMs）是肿瘤的炎症微环境与肿瘤细胞间的重要信使。它是从血液中的单核细胞演变而来,主要通过集落刺激因子（ Colony -stimulating factor , CSF）趋化至肿瘤组织中。本文简述了TAMs通过影响血管生成和淋巴管生成,抑制免疫,调节基质,与干细胞相互作用等方面促进肿瘤的进展。分析表明靶向于TAMs的治疗策略是未来治疗肿瘤的一个新方向。     

Cancer stem cells: beyond Koch's postulates

Until the last century, infectious diseases were the leading cause of human mortality. Therefore, our current medical reasoning is profoundly influenced by views that originated from medical microbiology. The notion that cancer growth is sustained by a sub-population of particular cells, the cancer stem cells, is highly reminiscent of the germ theory of disease as exemplified by Koch's postulates in the XIXth century. However, accumulating data underscore the importance of cell-cell interactions and tumor environment. Hence it is essential to critically review the basic tenets of the cancer stem cell concept on the light of their relationships with Koch's postulates. Shifting the pathogenic element from a special cellular entity (cancer stem cell or microorganism) to a "pathogenic field" could be critical for curing both cancer and drug-resistant infectious diseases.     

The cultivation and identification of tumor stem cells from neuroblastoma derived tumor spheres

Background and Objective: Since the proposal of the tumor stem cell hypothesis, considerable interest has been devoted to the isolation and purification of tumor stem cells. Tumor stem cell enrichment from primary tumor derived cell spheres has been demonstrated in specific, serum-free media. This goal of this study is to establish a method of cultivating floating tumor spheres from neuroblastoma cells and to confirm that neuroblastoma spheres are rich in tumor stem cells. Methods: Bone marrow aspirates wer...     

Cancer stem cells in human gastrointestinal cancer

Cancer stem cells (CSCs) are thought to be responsible for tumor initiation, drug and radiation resistance, invasive growth, metastasis, and tumor relapse, which are the main causes of cancer‐related deaths. Gastrointestinal cancers are the most common malignancies and still the most frequent cause of cancer‐related mortality worldwide. Because gastrointestinal CSCs are also thought to be resistant to conventional therapies, an effective and novel cancer treatment is imperative. The first reported CSCs in a gastrointestinal tumor were found in colorectal cancer in 2007. Subsequently, CSCs were reported in other gastrointestinal cancers, such as esophagus, stomach, liver, and pancreas. Specific phenotypes could be used to distinguish CSCs from non‐CSCs. For example, gastrointestinal CSCs express unique surface markers, exist in a side‐population fraction, show high aldehyde dehydrogenase‐1 activity, form tumorspheres when cultured in non‐adherent conditions, and demonstrate high tumorigenic potential in immunocompromised mice. The signal transduction pathways in gastrointestinal CSCs are similar to those involved in normal embryonic development. Moreover, CSCs are modified by the aberrant expression of several microRNAs. Thus, it is very difficult to target gastrointestinal CSCs. This review focuses on the current research on gastrointestinal CSCs and future strategies to abolish the gastrointestinal CSC phenotype.     

Thyroid hormone as a regulator of tumor induced angiogenesis

Thyroid hormones (TH) – 3,5,3′-triiodo-l-thyronine (T₃) and l-thyroxine (T₄) – are important regulators of differentiation, growth, metabolism, and physiological function in most tissues. TH have been also implicated in cellular transformation, tumorigenesis and metastasis, assuming particular importance in tumor induced angiogenesis. TH-induced angiogenesis is thought to be initiated at integrin αvβ3 membrane receptor mainly through T₄ binding. The reduction of TH in circulation or the inhibition of TH actions at the integrin αvβ3 receptor would consequently produce a reduction on the proliferative and angiogenic TH effects. Therefore, targeting TH actions could be an alternative adjuvant therapy against cancer proliferation and angiogenesis.     

肿瘤干细胞研究进展

近年提出的肿瘤干细胞（TSC）学说认为肿瘤组织中存在极少量具有干细胞性质的癌细胞亚群,具有多向分化潜能和无限增殖及自我更新能力,是肿瘤发生、发展、侵袭、转移、复发及耐药的决定性因素。目前已在部分肿瘤分离鉴定出TSC的存在。TSC学说的提出将为最终根治肿瘤提供新靶点。     

Medulloblastoma stem cells: Modeling tumor heterogeneity

Brain tumors represent the leading cause of childhood cancer mortality, with medulloblastoma (MB) being the most frequent malignant tumor. In this review we discuss the morphological and molecular heterogeneity of this malignant childhood brain tumor and how this key feature has implicated the presence of a MB stem cell. We focus on evidence from cerebellar development, histopathological and molecular subtypes of MB, the recent identification of brain tumor-initiating cells (BTICs, also referred to as MB stem cells), and the current limitations in studying the interplay between MB stem cells and tumor heterogeneity.     

Cancer stem cells in hepatocellular carcinoma: Recent progress and perspective

Although the “cancer stem cell (CSC)” hypothesis was first proposed roughly 50 years ago, recent progress in stem cell biology and technologies has successfully achieved the identification of CSCs in a variety of cancers. CSCs are defined as a minor population which possesses a prominent ability to generate new tumors that faithfully reproduce the phenotype of original tumors in xenotransplant assays. Additionally, CSCs are able to self-renew and generate differentiated progenies to organize a hierarchical cell system in a similar fashion to normal stem cells. Although not all types of cancer follow the CSC theory, it provides an attractive cellular mechanism to account for the therapeutic resistance and recurrence of the disease. A minor population with CSC properties has been detected in a number of established hepatocellular carcinoma (HCC) cell lines and extensive analyses characterizing the CSC system in primary HCC samples are now ongoing. Considering that HCC has high rates of recurrence and mortality, novel therapeutic approaches are urgently required. Although the clinical relevance of CSCs remains elusive, deep understanding of the cellular organization of HCC may allow us to develop therapies targeting specific cell types such as CSCs.     

缺氧对肿瘤干细胞的影响

氧是生命体维持能量代谢和各种生命活动的必需元素，在于细胞功能调控中发挥重要的作用。缺氧是实体瘤组织的重要特征：最近的一系列研究表明缺氧是肿瘤干细胞发生和转移的重要环节，这一思路丰富了人们对肿瘤干细胞局部微环境调控机制的认识，也为肿瘤的靶向治疗提供了新的线索。     

缺氧对肿瘤干细胞的影响

氧是生命体维持能量代谢和各种生命活动的必需元素，在于细胞功能调控中发挥重要的作用。缺氧是实体瘤组织的重要特征：最近的一系列研究表明缺氧是肿瘤干细胞发生和转移的重要环节，这一思路丰富了人们对肿瘤干细胞局部微环境调控机制的认识，也为肿瘤的靶向治疗提供了新的线索。     

肿瘤干细胞在肿瘤血管生成中的作用

 肿瘤干细胞（CSC）在肿瘤血管生成中有重要作用,血管生成因子、乏氧等介导了这一过程。CSC能分化成血管内皮细胞,并且参与血管生成拟态的形成,这可能是肿瘤启动和进展的关键因素之一。深入研究CSC在肿瘤血管生成中的作用对肿瘤的靶向治疗有重大意义。     

Human renal cancer stem cells

Cancer stem cells (CSCs), isolated in renal carcinomas, exhibit tumor-initiating capabilities and pluripotency. No specific CSC markers have been identified so far; therefore, their characterization is mainly based on functional studies. As they are resistant to chemo and radio therapy, renal CSCs may have a relevant role in tumor establishment, progression, and recurrence. CSCs were also shown to contribute to intra-tumor vasculogenesis through an endothelial differentiation and to favor the generation of the pre-metastatic niche through the release of exosomes/microvesicles.