Urinary vascular endothelial growth factor and its correlation with bladder cancer recurrence rates

PURPOSE: Vascular endothelial growth factor (VEGF) is a principal growth factor mediating tumor angiogenesis. The high expression of VEGF within bladder tumors is associated with a poor prognosis. We quantified urinary VEGF and determined its potential as a prognostic marker in bladder cancer. MATERIALS AND METHODS: VEGF was measured by enzyme-linked immunosorbent assay in the urine of 261 patients, including 153 undergoing cystoscopic surveillance for bladder cancer and 108 with another advanced malignancy or a benign urological condition. The source of urinary VEGF was studied through its quantification in bladder tumors and normal bladders. RESULTS: Urinary VEGF was higher in patients undergoing cystoscopic surveillance for bladder cancer than in those with an advanced nonbladder malignancy (p <0.0001) or a benign urological condition (p = 0.004). The highest levels were noted in patients with bladder cancer compared to those with clear cystoscopy (p <0.0001). In 26 cases the correlation between VEGF protein levels in bladder cancer and urine (r = 0.67, p = 0.003) suggested that the tumor is a source of urinary VEGF. Increased VEGF protein in normal urothelium in 22 patients with bladder cancer compared to that in 7 cadaveric organ donors (p = 0.002) indicates that urinary VEGF may also be derived from nonmalignant urothelium. In 61 cases we established a correlation between urinary VEGF and stage T1 or less superficial bladder tumor recurrence rates (r = 0.45, p <0.0001). CONCLUSIONS: Our study demonstrates that VEGF is high in the urine of patients with bladder cancer and it correlates with tumor recurrence rates. VEGF is implicated in the pathogenesis of bladder cancer recurrence. Its quantification may provide a valuable noninvasive marker for the early detection of bladder tumor recurrence as well as a therapy target.     

Different isoform patterns for vascular endothelial growth factor between clear cell and papillary renal cell carcinoma

OBJECTIVE: To investigate the protein expression of vascular endothelial growth factor (VEGF) isoforms in relation to the clinical course in patients with different renal cell carcinoma (RCC) types, as angiogenesis is essential for tumour growth and metastasis. PATIENTS AND METHODS: Western blots were assayed of protein extracts from tumour and concomitant kidney cortex samples from 96 patients. The levels of VEGF189, VEGF165, and VEGF121 isoforms were correlated with clinicopathological characteristics and survival. RESULTS: VEGF189 levels were significantly higher in kidney cortex and chromophobe RCC than in papillary and conventional RCC. In papillary RCCs, VEGF189 levels correlated inversely with tumour stage and tumour size. VEGF165 levels were higher in kidney cortex than in RCC, but there was no difference among the RCC types. VEGF121 expression was associated with less advanced tumour stage in conventional RCC. Using multivariate analysis, VEGF189 remained as an independent prognostic factor for patients with papillary RCC. CONCLUSIONS: VEGF189 was associated with tumour progression; in papillary RCC, VEGF189 was a significant independent prognostic factor. VEGF protein isoform patterns differed among the specific RCC types. Additional knowledge is essential to design new anti-angiogenic therapies for all RCC types.     

肿瘤组织VEGF表达和MVD与膀胱癌预后的关系

目的:探讨肿瘤组织中血管内皮生长因子(Vascular endothelial growth factor,VEGF)表达和微血管密度(Microvessel density,MVD)与膀胱癌预后的关系。方法:采用免疫组织化学方法检测62例膀胱癌手术标本中VEGF和MVD。结果:VEGF阳性表达率为63%,VEGF阳性表达的肿瘤组织中的MVD明显高于阴性者(P<0.01);VEGF表达和MVD与肿瘤的浸润生长、血行转移、淋巴结转移具有明显相关关系(P<0.05,P<0.01);VEGF阳性表达者的预后较阴性者差;多因素分析表明,VEGF和MVD可能成为判断膀胱癌预后的新因素。结论:VEGF表达和MVD与膀胱癌的恶性进程和不良预后有关,测定VEGF和MVD可能是判断膀胱癌预后有价值的指标。     

Vascular endothelial growth factor as prognostic factor in renal cell carcinoma

PURPOSE: Vascular endothelial growth factor (VEGF) has been recognized as an important constituent of vascularization and growth of solid tumors. Serum VEGF levels were evaluated and correlated to clinicopathologic findings and clinical outcome in patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: Serum samples were collected before surgery in 164 patients with RCC. Levels of VEGF165 protein in sera were measured using a quantitative ELISA. Univariate and multivariate analyses were performed. RESULTS: The VEGF165 level in serum was significantly increased (p = 0.0001) in patients with RCC (median 343.4 pg./ml.) compared with the control patients (median 103.8 pg./ml.). The level of VEGF165 in serum correlated to clinical stage and histopathological grade. Patients with VEGF165 levels below median value had significantly longer survival time than patients with higher levels (p = 0.0001). This was also shown when VEGF165 was analyzed in univariate Cox regression (p = 0.0001). The impact of VEGF165 on survival was especially shown in patients having tumors with vein invasion (pT3b-c N0 M0) and in patients with clinical stages I - III (p = 0.0240 and p = 0.0023, respectively). When using multivariate analysis, only tumor stage and grade remained as independent prognostic variables. CONCLUSIONS: In RCC, serum VEGF165 level was significantly correlated to tumor stage and grade. Increased levels were correlated to adverse survival. Although, VEGF did not remain as an independent prognostic factor in multivariate analysis the levels of VEGF165 in serum was found useful for the identification of patients with potentially progressive disease especially for those with vein invasion.     

Expression and significance of vascular endothelial growth factor receptor 2 in bladder cancer

PURPOSE: Vascular endothelial growth factor has a critical role in maintaining tumor microvasculature and, as such, is an attractive target for anti-angiogenic therapy. Aberrant expression of VEGF receptors, especially VEGFR2, on epithelial tumor cells allows VEGF to stimulate growth and migration of tumor cells in an autocrine and/or paracrine manner. Therefore, we studied the expression of VEGF and VEGFR2 in bladder cancer, and the relationship to disease characteristics. MATERIALS AND METHODS: Expression of VEGF and VEGFR2 was studied in a cohort of 72 patients with transitional cell cancer of the bladder. Tumor tissues from all patients were analyzed by immunohistochemistry and examined by a pathologist blinded to patient outcome. Patient demographics and disease outcome were correlated with expression of these markers. Bladder cancer cell lines that express VEGFR2 were studied in vitro and in vivo to establish the significance of VEGF/VEGFR2 signaling. RESULTS: Expression of VEGF and VEGFR2 was observed in 58% and 50% of urothelial tumor cells, respectively. VEGF expression failed to correlate with clinical variables. However, VEGFR2 expression correlated with disease stage (coefficient 0.23, p = 0.05). In addition, VEGFR2 expression increased with tumor invasion into the muscle (p <0.01). Experiments with VEGFR2 positive bladder cancer cell lines in vitro demonstrated increased invasion in response to VEGF. In addition, VEGF inhibition augmented the effect of docetaxel in a murine xenograft model of bladder cancer with a significant inhibition in proliferative index and microvascular density, and induction of apoptosis. CONCLUSIONS: Increased VEGFR2 expression correlates with several features that predict progression of urothelial cancer, including disease stage and invasive phenotype. VEGF targeted therapy may enhance the efficacy of standard therapy for bladder cancer.     

浅表性膀胱癌PD-ECGF mRNA表达的意义

目的　探讨浅表性膀胱癌中血小板衍化内皮细胞生长因子 (PD ECGF)mRNA表达的意义。方法　用逆转录多聚酶链反应 (RT PCR)分析了 2 8例浅表性膀胱癌和 6例正常膀胱粘膜的PD ECGFmRNA表达 ,并分析了PD ECGFmRNA表达与浅表性膀胱癌的固有层浸润及复发之间的关系。结果　所有标本均见不同程度的PD ECGFmRNA表达 ,粘膜固有层浸润的pT1期膀胱癌的PD ECGFmRNA表达是正常膀胱粘膜的 3 1倍 (t=2 13,P <0 0 5 ) ,是乳头状非浸润性膀胱癌 (pTa期 )的 2 2倍 (t=2 6 6 ,P <0 0 5 ) ;G3 级膀胱癌中PD ECGFmRNA表达是正常膀胱粘膜的 3 3倍(t=2 4 4 ,P <0 0 5 ) ,是G1 2 级膀胱癌的 2 5倍 (t=3 36 ,P <0 0 1)。全部病例获得随访 ,平均随访18个月 ,共复发 11例 ,复发者膀胱癌的PD ECGFmRNA水平是未复发者的 3倍 (t=4 4 9,P <0 0 1) ,用PD ECGFmRNA水平预测本组膀胱癌复发的敏感性为 81 8% ,特异性为 82 4 %。结论　PD ECGFmRNA表达不仅与浅表性膀胱癌的分化程度有关 ,而且在膀胱癌的早期浸润中起着重要作用 ,测定PD ECGFmRNA表达对判断浅表性膀胱癌的分化程度、固有层浸润与复发有一定意义。     

The expression of vascular endothelial growth factor in transitional cell carcinoma of urinary bladder is correlated with cancer progression

Vascular epithelial growth factor (VEGF) regulates neovascualrization in malignant cells. VEGF as a mitogen is thought to alter cancer cell formation and tumor progression. We aimed to investigative the expression of the VEGF gene to evaluate their clinical significance in transitional cell carcinoma (TCC) of urinary bladder. Tissue samples from 161 patients with TCC were examined with an immunohistochemical stain for the expression of the VEGF gene. The expression rate was compared to 32 normal bladder mucosal samples obtained from transurehtral surgery from noncancer patients. The results revealed significant differences between normal urothelium (0%) and cancer tissue (54.7%) for the positive staining of VEGF protein (P < 0.001). With the progression of tumor grade and clinical staging, the positive rate of VEGF gene expression significantly increased. Expression of the VEGF gene in the invasive group was greater than that in the noninvasive group (P < 0.001). The results revealed that expression of the VEGF gene is proportional to the formation and progression of TCC. Therefore, abnormal expression of VEGF genes can be used as a prognostic marker in TCC of urinary bladder.     

Prognostic significance of platelet-derived endothelial cell growth factor/thymidine phosphorylase expression in stage pT1 G3 bladder cancer

BACKGROUND: The management of patients with pT1 G3 bladder cancer remains controversial because of the high incidence of recurrence with muscle invasion. Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and has angiogenic activity. The aim of this study was to determine whether the expression of PD-ECGF/dThdPase in bladder cancer tissue was associated with tumor progression and recurrence in patients with pT1 G3 bladder cancer. METHODS: Fifteen patients who were pathologically diagnosed as having pT1 G3 transitional cell carcinoma of the bladder were treated with transurethral resection. Sections of paraffin-embedded bladder tissue were immunohistochemically stained with either mAb654-1, a monoclonal antibody against human PD-ECGF or anti-CD34 monoclonal antibody, respectively. When more than 10% of tumor cells were positively stained with mAb654-1, this section was defined as positive in this study. RESULTS: Eight of 15 sections from patients with pT1 G3 bladder cancer (53%) were positive with PD-ECGF/dThdPase. During follow up, patients in the negative group had no disease progression and only two patients had local recurrence. In contrast, seven of eight positives had recurrence (P < 0.05) and progression was also observed in four recurrent patients. However, there was no statistical relationship between PD-ECGF and CD34 expression in any of the patients. CONCLUSION: The expression of PD-ECGF/dThdPase appears to be an important prognostic factor of pT1 G3 bladder cancer and did not show any significant relationship between PD-ECGF/dThdPase expression and vascular density.     

血管生成在肝门部胆管癌发生发展中作用的研究

目的　探讨血管内皮细胞生长因子 (vascularendothelialgrowthfactor,VEGF)和血管生成与肝门部胆管癌发生发展的关系。方法　应用逆转录多聚酶链反应 (RT PCR)和免疫组化技术对2 6例肝门部胆管癌、癌周组织及 12例正常组织中VEGFmRNA和蛋白及微血管密度 (MVD)进行检测。结果　 2 6例肝门部胆管癌组织中VEGFmRNA阳性表达率为 77% (2 0 / 2 6 ) ;癌周组织阳性表达率为2 7% (7/ 2 6 ) ;正常组织表达率为 8% (1/ 12 ) ,三者差异有显著性 (P <0 0 1)。VEGFmRNA阳性表达与VEGF蛋白表达具有一致性 ;VEGFmRNA阳性者MVD值显著高于阴性者 (P <0 0 1) ;VEGFmRNA表达和MVD与肝门部胆管癌的分化程度、浸润转移密切相关 (P <0 0 5 ) ,而与肿瘤发生部位、病理类型、大小、临床分型无关 (P >0 0 5 )。结论　VEGF在肝门部胆管癌的发生和浸润转移过程中发挥重要作用 ,肿瘤血管生成与肝门部胆管癌浸润转移密切相关。     

化疗栓塞对膀胱肿瘤新生血管生成及血管内皮细胞生长因子表达的影响

目的 探讨膀胱动脉化疗栓塞对膀胱肿瘤新生血管生成及血管内皮细胞生长因子(VEGF)表达的影响. 方法 膀胱癌患者30例.临床分期Tis1例、Ta2例、16例、T2 11例、T39例、T41例.病理分级G19例、G213例、G38例.采用丝裂霉素20 mg或羟喜树碱10 mg联合顺铂60 mg经膀胱动脉灌注及明胶海绵栓塞.化疗栓塞前后膀胱镜下取肿瘤组织,免疫组织化学SP法测定VEGF表达及微血管密度(MVD),并进行病理观察及随访. 结果 化疗栓塞前后肿瘤VEGF阳性表达率分别为73.33%(22例)及43.33%(13例); MVD分别为69.81±3.38及56.35±3.26,差异均有统计学意义(P<0.05).病理观察栓塞前后瘤体直径分别为(2.17±0.88)及(1.58±0.87)cm,差异有统计学意义(P<0.05).化疗栓塞后肿瘤组织明显坏死、退变.30例随访12～36个月,平均24.6个月,5例复发(G1T1、G2T1、G2T3、G3T3、G3T4各1例,单纯移行细胞癌4例、混合癌1例),复发时间为栓塞后6个月1例.6～12个月2例,24～36个月2例.复发组栓塞前后VEGF阳性分别为5例(均为强阳性)及4例(阳性3例、强阳性1例),差异无统计学意义(P>0.05),但强阳性表达差异有统计学意义(P<0.05),MVD值分别为87.35±2.96、72.37±4.11,差异有统计学意义(P<0.05).未复发组栓塞后MVD值为53.15±3.50,与复发组比较差异有统计学意义(P<0.05).结论 化疗栓塞能降低膀胱癌组织VEGF表达,减少MVD计数,提示化疗栓塞可影响膀胱癌的分化程度,使肿瘤降级降期,减少术后转移,降低复发率,提高生存率.     

Significance of vascular endothelial growth factor and epidermal growth factor in development of papillary thyroid cancer

Background and aims Vascular endothelial growth factor (VEGF) induces proliferation of endothelial cells, stimulates angiogenesis and increases vascular permeability. Epidermal growth factor (EGF) induces proliferation of epidermal cells and stimulates epidermal migration. Increased VEGF and EGF expression have been associated with poor clinical outcome in many malignancies. Several recent reports have shown overexpression of VEGF and EGF in papillary thyroid cancer (PTC). The study aimed to determine the intensity of expression of VEGF and EGF in patients with PTC and to find any correlation between the intensity of the expression and staging of the disease at the moment of surgeryPatients and methods The study comprised a group of 48 consecutive patients with PTC who underwent radical surgery. The group consisted of 11, 25, eight and four patients at pT1N0M0, pT2N0M0, pT3N1M0 and pT4N1M0 stages, respectively. The control group was composed of 20 healthy bone marrow transplant donors, age-, gender- and BMI-matched with PTC patients. The immuno-chemiluminescence enzyme linked immunoassay (ELISA) method was used to determine the expression and level of VEGF and EGF in serum samples. Patients characteristics, serum levels of VEGF and EGF, final histology and pTNM were analysed.Results The mean serum level of VEGF and EGF was remarkably higher in PTC patients than in controls. A negative correlation between staging in pTNM classification and the mean serum VEGF level (r=–0.5168; P<0.05) as well as a positive correlation between staging in pTNM classification and the mean serum EGF level (r=0.6104; P<0.05) in PTC patients was observed.Conclusions Both VEGF and EGF play an important role in PTC growth. However, the intensity of their expression is variable, depending on the stage of the disease. The highest intensity of VEGF expression is characteristic for low-stage T1N0M0 disease, whereas the highest intensity of EGF expression is more often found at locally advanced pT3 and pT4N1M0 stages of the disease. Further long-term follow-up studies are required to demonstrate the prognostic value of VEGF and EGF in PTC, particularly in identification of patients with expected poor prognosis or shorter recurrence-free survival.The paper was presented at the First Constituent Congress of the European Society of Endocrine Surgeons, 14–15 May 2004, Pisa, Italy     

血小板衍化内皮细胞生长因子/胸腺嘧啶磷酸酶和血管内皮生长因子在间质性膀胱炎诊断中的应用

目的 检测血小板衍化内皮细胞生长因子/胸腺嘧啶磷酸酶(PDECGF/TP)和血管内皮生长因子(VEGF)的表达,探讨血管生长因子在间质性膀胱炎(IC)患者膀胱中的表达活性与膀胱镜下的表现及临床症状的关系.方法 选择符合NIH/NIDDK诊断标准的IC患者12例为实验组和12例Ⅲ型前列腺炎患者为对照组.实验组行麻醉下水扩张,膀胱组织活检,常规苏木素-伊红(HE)染色观察肥大细胞数量.应用免疫组织化学检测PDECGF/TP和VEGF表达,进行免疫组织化学阳性细胞计数及免疫组织化学评分(IHS).结果 实验组12名患者在麻醉下水扩张时发现膀胱黏膜点片状出血.常规HE染色病理切片观察可见IC组膀胱组织标本中肥大细胞数目明显高于对照组(P＜0.05),且IC患者的肥大细胞多存在于膀胱组织的黏膜下层,而对照组膀胱组织仅偶见肥大细胞.实验组患者膀胱黏膜PDECGF/TP和VEGF阳性细胞百分比计数、阳性细胞染色强度及HIS评分明显高于对照组(P＜0.05).结论 IC患者血管生长因子PDECGF/TP和VEGF呈高水平表达,通过检测PDECGF/TP和VEGF能够筛选或确诊间质性膀胱炎.

Abstract：

Objective To find out the relationship among the expression of vascular growth factors in patients with interstitial cystitis (IC) and their performance under the cystoscopy as well as the clinical symptoms by detecting the expression of platelet-derived endothelial growth factor/thymine phosphatase (PDECGF/TP) and vascular endothelial growth factor (VEGF). Methods Twelve cases of IC served as the experimental group and 12 cases of type Ⅲ as the control group. The patients in experimental group had bladder mucosa biopsy. The number of mast cells was observed by HE staining. The expression of PDECGF/TP and VEGF and immunohistological score (IHS) were detected by using immunohistochemistry. Results Bladder mucosa hemorrhage points and sheets were observed under water expansion. The number of mast cells existing in the submucosa of the bladder tissue was significantly greater than in control group (P ＜ 0. 05 ). The percentage of PDECGF/TP and VEGF positive cells and IHS in experimental group were significantly higher than in control group (P ＜ 0. 05). Conclusion The expression of PDECGF/TP and VEGF was up-regulated in patients with IC. IC can be screened out or diagnosed by detecting PDECGF/TP and VEGF.     

Clinical significance of preoperative serum vascular endothelial growth factor levels in patients with colorectal cancer and the effect of tumor surgery

BACKGROUND: Vascular endothelial growth factor (VEGF) is an angiogenic cytokine involved in the progression of solid tumors. In this study we evaluated the clinical usefulness of preoperative serum VEGF concentrations in patients with colorectal cancer. The changes in serum VEGF levels after tumor surgery were also evaluated. METHODS: Serum VEGF levels were determined by an enzyme-linked immunosorbent assay in the sera of 61 healthy control subjects and 67 patients with colorectal cancer preoperatively and 7 and 30 days after surgery. RESULTS: Serum VEGF levels in patients with colorectal cancer (median, 492 pg/mL; interquartile range, 281 to 737 pg/mL) were higher (P <.0001) than in control subjects (median, 186 pg/mL; interquartile range, 100 to 273 pg/mL). There was a significant association between serum VEGF levels and disease stage, invasion depth of the tumor, the presence of lymph node and distant metastases, and the degree of differentiation. Curative but not palliative resection of the primary tumor resulted in a significant decrease of preoperative serum VEGF levels but normalized in only 72% of patients. Failure of a return of VEGF to normal after resection for cure was associated with an increased although not statistically significant risk of metastasis during follow-up. Univariate analysis showed a lower survival rate for patients with increased preoperative serum VEGF levels (P <.002). Multivariate regression analysis showed that the prognostic value of serum VEGF level was not independent of tumor stage. CONCLUSIONS: These findings suggest that VEGF plays an important role in tumor progression and the formation of distant metastases in colorectal cancer. It is at present unclear whether serial estimation of serum VEGF is clinically useful in the prediction of tumor relapse.     

血管内皮生长因子及其受体mRNA在乳腺癌组织中的表达

目的　研究血管内皮生长因子及其受体FLT 1、FLK 1mRNA在乳腺癌组织中的表达及与临床病理因素的相关性。　方法　采用逆转录聚合酶链反应技术对手术的 47例乳腺癌标本 ,11例乳腺良性病变标本中血管内皮生长因子 (VEGF)及其受体FLT 1、FLK 1mRNA的表达进行检测。结果　在良、恶性乳腺组织中均检测到VEGF12 1、165mRNA的表达 ,在乳腺癌组织中表达水平分别为0 42 0± 0 13 3、0 2 91± 0 0 94高于良性乳腺组织 0 196± 0 0 67(P =0 0 0 0 )、0 2 0 6± 0 0 5 8(P =0 0 0 1) ;在乳腺癌组织中 ,VEGF12 1mRNA表达高于VEGF165mRNA(P =0 0 0 0 ) ,而在良性乳腺组织中两者表达水平差异无显著性意义 (P =0 666)。FLT 1、FLK 1mRNA在部分乳腺癌组织中表达 ,分别为 3 8 3 %(18/4 7)和 2 5 5 % (12 /4 7) ,而在良性乳腺组织中未见表达。乳腺癌组织中VEGF12 1、VEGF165、FLT 1、FLK 1mRNA表达与患者年龄、肿块大小、淋巴结转移状况、肿瘤分期及雌、孕激素受体状况之间无明显相关性。　结论　乳腺癌组织中VEGF12 1、165及其受体FLT 1、FLK 1mRNA表达水平上调 ,提示其在乳腺癌的血管生成中起着重要作用。     

膀胱移行细胞癌血管内皮生长因子的表达及临床意义

目的探讨血管内皮生长因子与膀胱癌浸润及复发的关系。方法应用ＬＳＡＢ免疫组织化学技术检测４０例膀胱移行细胞癌血管内皮生长因子（ＶＥＧＦ）的表达。结果膀胱癌细胞ＶＥＧＦ的表达率为５５％（２２／４０）,浸润性癌组ＶＥＧＦ的表达显著高于表浅性癌组（Ｐ＜０．０１）,有淋巴结转移癌组显著高于无转移癌组（Ｐ＜０．０５）,复发性癌组较初发性癌组差异有显著性（Ｐ＜０．００１）。结论ＶＥＧＦ可作为判断膀胱癌生物学行为的指标之一。     

Glucose-regulated protein 78 silencing down-regulates vascular endothelial growth factor/vascular endothelial growth factor receptor 2 pathway to suppress human colon cancer tumor growth

Background

Up to 20% of colorectal cancer (CRC) is diagnosed with distant metastasis. The combination of chemotherapy with anti-vascular endothelial growth factor (VEGF) antibody can improve patient survival. Glucose-regulated protein 78 (GRP78) has an important role in cancer progression, but little is known about its role in VEGF production in CRC. The aim of this study was to explore the mechanism of GRP78 in two human colon cancer cell lines.

Methods

We first checked the expression of GRP78 in human normal and colon cancer tissues and two colon cancer cell lines. Glucose-regulated protein 78 was knocked down using GRP78 small interfering RNA (siRNA) in HT29 and DLD-1 cells. We examined knockdown cells by the cell growth kinetics in vitro and tumor growth rate in vivo, respectively. We also investigated the effect of GRP78 siRNA on the expression of hypoxia inducible factor (HIF-1α), VEGF, and VEGF receptor 2 (VEGFR2).

Results

Compared with their adjacent normal tissue, we detected high expression levels of GRP78 of surgically removed colon cancer tissues. Using GRP78 siRNA, we reduced the expression of GRP78 in HT29 and DLD-1 cells. The GRP78 knockdown cells had a lower proliferation rate with fewer colony-forming units in vitro and produced smaller tumors in vivo. In dissecting the mechanism underlying the reduced cell growth, we found that the down-regulation of GRP78 decreased the production of HIF-1α, VEGF, and VEGFR2 and suppressed angiogenesis.

Conclusions

Silencing GRP78 not only inhibits tumor, but also decreases the expression of VEGF and VEGFR2. Collectively, therapy targeting for GRP78 may inhibit the formation of colon cancer tumors via the HIF-1α/VEGF/VEGFR2 pathway.