VEGF-RII influences the prognosis of pancreatic cancer
VEGF-RII influences the prognosis of pancreatic cancer
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DOI：
10.1097/01.sla.0000036262.67458.e7
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发表时间：
2002-12-01
影响因子：
9
通讯作者：
Hines, OJ
中科院分区：
文献类型：
--
作者：
Büchler, P;Reber, HA;Hines, OJ
目的探讨血管内皮生长因子（vascular endothelial growth factor，VEGF）通路是否可作为胰腺癌有效治疗的靶点。背景资料VEGF及其受体（VEGF-RI和-RII）是肿瘤新生血管形成的主要调节因子，是肿瘤生长和进展的关键因素。然而，血管内皮生长因子受体的表达一直被认为是有限的内皮细胞，限制了靶向治疗胰腺cancer.Methods蛋白定位和mRNA在胰腺癌标本，正常胰腺，人胰腺癌细胞系，和内皮细胞系进行了研究。通过[H-3]胸苷摄取测定细胞增殖。两种VEGF受体均通过反义技术在遗传上消除。结果VEGF-RI mRNA和VEGF-RII mRNA在24例胰腺癌中分别有17例和15例表达。VEGF受体不仅存在于血管中，也存在于胰腺癌细胞中。VEGF-RII表达与肿瘤分化差相关，与生存率差相关，而VEGF-RI表达不相关。VEGF治疗导致广泛的生长刺激，在六个胰腺癌细胞系，这是完全抑制反义治疗对VEGF-RII。脂质体介导的基因转移在裸鼠胰腺癌显着降低局部肿瘤生长和转移性tumor spread.Conclusions VEGF/VEGF-RII途径调节血管生成和局部肿瘤生长和扩散在胰腺癌。VEGF-RII的基因靶向阻断胰腺癌细胞在体内的局部生长和转移扩散，因此为患有这种疾病的患者提供了潜在的新治疗选择。
Objective To evaluate whether the vascular endothelial growth factor (VEGF) pathway can be used as a target for effective treatment of pancreatic cancer.Summary Background Data VEGF and its receptors (VEGF-RI and -RII) are the predominant regulators of tumor neoangiogenesis, a key element for tumor growth and progression. However, VEGF receptor expression has been thought to be limited to endothelial cells, limiting the possibility of targeting it for therapy of pancreatic cancer.Methods Protein localization and mRNA were studied in pancreatic cancer specimens, normal pancreas, human pancreatic cancer cell lines, and an endothelial cell line. Cell proliferation was determined by [H-3] thymidine uptake. Both VEGF receptors were genetically eliminated by antisense technology. The same approach was used in a murine model of pancreatic cancer in a therapeutic approach.Results VEGF-RI mRNA and VEGF-RII mRNA were expressed in 17 and 15 of 24 pancreatic cancer samples, respectively. VEGF receptors were found not only in blood vessels but also in pancreatic cancer cells. VEGF-RII expression correlated with poor tumor differentiation and was associated with poorer survival, while VEGF-RI expression did not correlate. VEGF treatment led to extensive growth stimulation in six of seven pancreatic cancer cell lines, which was completely inhibited by antisense treatment against VEGF-RII. Liposome-mediated gene transfer in nude mice with pancreatic tumors markedly reduced local tumor growth and decreased metastatic tumor spread.Conclusions The VEGF/VEGF-RII pathway regulates angiogenesis and local tumor growth and spread in pancreatic cancer. Genetic targeting of VEGF-RII blocks local growth and metastatic spread of pancreatic cancer cells in vivo and therefore offers a potential new therapeutic option for patients with this disease.