促红细胞生成素及其受体在肿瘤发生发展中的作用

研究发现,促红细胞生成素(EPO)及EPO受体(EPOR)在多种恶性肿瘤组织中表达,且EPO能促进肿瘤微血管形成,刺激肿瘤细胞增殖,抑制凋亡,还调节肿瘤细胞对放化疔治疗的敏感性.另有研究表明,EPO的应用不利于肿瘤的控制和预后.EPO对肿瘤患者的疾病进展和生存期的影响仍需进一步研究.     

促红细胞生成素及受体在肿瘤中的研究进展

近年来,在多种非造血组织及肿瘤中发现了促红细胞生成素(EPO)及其受体。EPO对促红细胞生成的作用是已知的,然而,在肿瘤和非造血组织中,这种激素被认为可以刺激血管生成,促进细胞增殖,抑制细胞凋亡。本文主要阐述EPO在肿瘤中的作用及机制,总结EPO与肿瘤的相关性,为进一步研究EPO对肿瘤的影响提供理论依据。     

促红细胞生成素受体在食管癌组织中的表达及其与微血管密度的相关性

背景与目的:新近多项研究发现,促红细胞生成素受体(erythropoietinreceptor,EPO-R)在多种实体瘤中表达,EPO/EPO-R环路与肿瘤细胞的增殖、新生血管形成、侵袭特性相关。本研究旨在探讨食管癌组织中EPO-R的表达,及其与新生血管形成的关系。方法:采集食管癌标本110例,用免疫组化法检测癌组织中EPO-R蛋白的表达强度;并以Ⅷ因子相关抗原多克隆抗体(FⅧ-R Ag)标记血管内皮细胞,计算微血管密度(microvessel density,MVD),以此量化新生血管形成的程度。结果:110例食管癌组织中均表达EPO-R,EPO-R表达于食管癌细胞的胞浆和(或)胞膜。肿瘤分化级别高组与淋巴结转移组中EPO-R表达强度高;有淋巴结转移组MVD高于无淋巴结转移组(P<0.001),晚期患者(Ⅲ/ⅣA/ⅣB)MVD高于早期患者(Ⅰ/ⅡA/ⅡB)(P=0.022),有吸烟史组MVD高于无吸烟史组(P=0.029)。食管癌中EPO-R表达强度与MVD之间存在显著正相关(r=0.618,P<0.01)。结论:食管癌组织中普遍存在EPO-R的表达,EPO-R水平与食管癌血管生成程度和病情进展呈高度正相关。     

非小细胞肺癌组织中促红细胞生成素及其受体mRNA的表达及意义

目的 探讨促红细胞生成素（EPO）及其受体（EPO-R）在非小细胞肺癌（NSCLC）组织中的表达及与临床病理参数的关系。方法 采用逆转录-聚合酶链式反应（RT-PCR）检测31例NSCLC组织、相应的癌旁组织及21例肺良性病变组织中EPO和EPO-R的mRNA水平,并分析其水平与NSCLC临床病理参数的关系。结果 EPO-mRNA和EPO-R mRNA在NSCLC组织中的相对表达量分别为0.79±0.18和0.60±0.13,在癌旁组织中分别为0.23±0.09和0.17±0.09,在肺良性病变组织中分别为0.19±0.11和0.13±0.09。EPO mRNA和EPO-R mRNA 在NSCLC组织中的表达高于癌旁组织和肺良性病变组织,差异有统计学意义（P＜0.05）。EPO mRNA和EPO-R mRNA的表达与NSCLC的临床分期、病理分型及吸烟史均无关（P＞0.05）。结论 NSCLC中EPO／EPO-R mRNA 高表达,提示EPO／EPO-R可能参与肿瘤的发生过程,因此可将其表达水平作为NSCLC的辅助性诊断指标。     

重组人红细胞生成素治疗肿瘤相关性贫血临床应用分析

正1促红细胞生成素治疗肿瘤相关性贫血概述促红细胞生成素(erythropoietin,EPO)主要由肾脏的肾小管周围细胞产生,另有5%～10%的EPO由肝细胞或肝内的库普弗细胞产生。EPO主要作用于红系祖细胞阶段,随剂量加大,其作用可能     

EPO与EPO受体的研究进展

红细胞生成素（erythropoietin,EPO）是调节红细胞产生的必需的细胞因子,它与幼红细胞表面红细胞生成素受体（EPOR）结合后,EPOR形成二聚体,再通过JAK／STAT和Ras／MAP激酶等信号传导途径调节红系的增生和分化。近年来,在国外已有体外和动物实验报道,提示EPOR不仅存在于幼红细胞,在其他细胞也有发现,即认为EPO的作用不仅仅限于红系细胞。但没有证据表明外源性重组人红细胞生成素（r—HuEPO）能够促进肿瘤细胞增生。r—HuEPO在治疗ACD中起着重要作用,EPO／EPOR在人白血病细胞的作用尚需进一步地全面分析与研究。     

脑胶质瘤促红细胞生成素的表达及其生物学意义

目的　探讨人脑胶质瘤中促红细胞生成素 (erythropoietin,EPO)的表达 ,并研究其与肿瘤病理分级、Ki- 6 7、CD10 5的关系。方法　采用免疫组化 S- P法 ,检测 4 9例人脑胶质瘤中 EPO、Ki- 6 7、CD10 5的表达。结果　EPO的表达与肿瘤病理分级有关 (χ2 =15 .19,P<0 .0 1) ;与 Ki- 6 7、CD10 5的表达密切相关 (F 分别为 19.4 5、16 .4 2 ,P值均 <0 .0 1)。结论　 EPO的表达可作为判断脑胶质瘤恶性程度的一个重要指标。EPO能促进肿瘤细胞增殖和血管形成 ,促进肿瘤生长。     

佳林豪有奖征文通知

肿瘤相关性贫血(cancer-related anemia,CRA)是恶性肿瘤常见的伴随疾病之一。CRA产生的主要原因有肿瘤方面的因素(如失血、溶血、骨髓受侵犯)和针对肿瘤治疗方面的因素(如化疗的骨髓抑制作用、肿瘤放射治疗等)。从20世纪90年代开始,促红细胞生成素类药物成为治疗CRA的最重要方法。促红细胞生成素(erythropoietin,EPO)是临床上     

癌性贫血患者血清促红细胞生成素的检测及其临床意义

促红细胞生成素（erythropoietin,EPO）主要由肾脏近曲小管附近的细胞合成和分泌,是调节红细胞生成和成熟的最重要的细胞因子,而且具有阻止红系祖细胞凋亡的功能。临床上很多癌症患者处于贫血状态,其血清EPO浓度的临床意义究竟如何目前尚有争议。为进一步明确血清EPO水平和癌性贫血水平之间的关系,以指导临床上对这类贫血患者的处理,     

促红细胞生成素治疗肿瘤相关性贫血的研究进展

摘 要：贫血是恶性肿瘤常见的伴随疾病。肿瘤相关性贫血对患者存在较大的影响,可以降低患者生活质量、影响放化疗疗效等。促红细胞生成素（erythropoietin,EPO）是临床上治疗肿瘤相关性贫血的重要方式,其可提高患者血红蛋白水平、减少红细胞的输注、改善生活质量,但是使用EPO可以使血栓发生风险升高,关于是否影响患者总生存期、促进肿瘤转移等方面仍然存在争议。文章根据国内外相关文献,对EPO用于肿瘤相关性贫血患者的疗效及安全性进行总结。     

Autocrine/paracrine erythropoietin regulates migration and invasion potential and the stemness of human breast cancer cells

Recent studies suggest that erythropoietin (EPO) has pleiotropic effects in several cell types in addition to hematopoietic cells; however, the role of EPO-mediated cell signaling in nonhematopoietic cells, including in cancer cells, remains controversial. Here, we report our findings of autocrine/paracrine production of EPO by breast cancer cells and its functional significance. We detected a significant level of autocrine/paracrine EPO in the conditioned medium from the culture of SKBR3 breast cancer cells, particularly when the cells were cultured in hypoxia. Through knockdown of EPO and EPO receptor expression and experimental elevation of EPO receptor expression in SKBR3 breast cancer cells, we demonstrated novel roles of autocrine/paracrine EPO-mediated cell signaling in regulating migration and invasion potential and stemness-like properties of breast cancer cells.     

Erythropoietin biology in cancer.

Erythropoietin (Epo) has long been known to be the principal hematopoietic growth factor that regulates cellular proliferation and differentiation along the erythroid lineage. Recent studies have shown that Epo is a pleiotropic cytokine that is proangiogenic and exerts broad tissue-protective effects in diverse nonhematopoietic organs. Recombinant Epo (rEpo) has been widely used in the clinic to prevent or treat malignancy-associated anemia. A series of clinical trials have documented the efficacy of rEpo in reducing RBC transfusion requirements and improving quality of life in cancer patients, and a recent meta-analysis suggested a positive effect on survival. However, two randomized trials reported negative outcomes with rEpo, as patients in the rEpo arm fared worse than their placebo-treated counterparts with respect to progression-free survival. The expression of Epo receptor (EpoR) in cancer cells has raised the possibility that exogenous rEpo may exert direct effects on tumor cells associated with the potential for stimulation of proliferation, inhibition of apoptosis, or modulation of sensitivity to chemoradiation therapy. The presence of an autocrine-paracrine Epo-EpoR system in tumors and potential effects of Epo on tumor microenvironment and angiogenesis are consistent with a complex biology for Epo-EpoR signaling in cancer that requires further research. This review describes Epo and EpoR biology, focusing on the pleiotropic effects of Epo on nonhematopoietic tissues as well as the expression and function of EpoR in cancer cells.     

Erythropoietin and erythropoietin receptor coexpression is associated with poor survival in stage I non-small cell lung cancer.

PURPOSE: This study was designed to evaluate the prognostic effect of erythropoietin (EPO) and EPO receptor (EPO-R) expression in stage I non-small cell lung cancer (NSCLC) patients. EXPERIMENTAL DESIGN: EPO and EPO-R expression in 158 tumor samples from resected stage I NSCLC was evaluated using immunohistochemistry and tissue array technology. RESULTS: EPO-R and EPO were highly expressed in 20.9% and 35.4% of tumors, respectively. High EPO-R expression compared with negative or low-level expression was associated with a poor 5-year disease-specific survival (60.6% versus 80.8%; P = 0.01, log-rank test). High EPO expression compared with negative and low-level expression was associated with a trend toward a poor 5-year disease-specific survival (69.6% versus 80.4%; P = 0.13, log-rank test). A high level of EPO-R and EPO coexpression was associated with a poor 5-year disease-specific survival compared with other groups of patients (50.0% versus 80.0% survival at the end of follow-up; P = 0.005, log-rank test). In multivariate analysis for disease-specific survival, high-level EPO-R and EPO coexpression was an independent prognostic factor for disease-specific survival (hazard ratio, 2.214; 95% confidence interval, 1.012-4.848; P = 0.046). CONCLUSION: These results establish the pejorative prognostic value of EPO and EPO-R expression in early-stage resected NSCLC and suggest a potential paracrine and/or autocrine role of endogenous EPO in NSCLC aggressiveness.     

Glioblastoma multiforme cells: expression of erythropoietin receptor and response to erythropoietin

Erythropoietin (EPO) is a glycoprotein hormone that is a primary regulator of erythropoiesis. In erythroid cells, EPO binds to its receptor (EPOR) to stimulate growth, prevent apoptosis, and promote differentiation. Both EPO and EPOR have been found in many normal and tumor nonerythroid cell types. EPO has been reported to stimulate proliferation and inhibit apoptosis of cancer cells. In this study, we found that EPOR is expressed in brain tumors, glioma cell lines and explants, as well as, normal brain. EPO slightly stimulated the growth of serum-starved glioma cells. Furthermore, EPO increased the phosphorylation of AKT through the PI3K pathway in the glioma cells. It also increased the phosphorylation of ERK, c-jun, JNK, as well as, the expression of BCL-2 and BCL-xl in these cells. These results suggest that the EPO-EPOR pathway may promote glioma cell survival and could become a therapeutic target in brain tumors.     

Erythropoietin and erythropoietin receptor expression in human cancer

Erythropoietin (EPO) stimulates the growth of erythroblasts in the bone marrow (C. Lacombe and P. Mayeux, NEPHROL: DIAL: TRANSPLANT:, 14 (SUPPL: 2): 22-28, 1999). We report basal and hypoxia-stimulated expression of EPO and its receptor, EPOR, in human breast cancer cells, and we demonstrate EPO-stimulated tyrosine phosphorylation and the proliferation of these cells in vitro. In 50 clinical specimens of breast carcinoma, we report high levels of EPO and EPOR associated with malignant cells and tumor vasculature but not with normal breast, benign papilloma, or fibrocystic tissue. Hypoxic tumor regions display the highest levels of EPO and EPOR expression. Enhanced EPO signaling may contribute to the promotion of human cancer by tissue hypoxia.