Influence of hypoxia and neoangiogenesis on the growth of pancreatic cancer.
Influence of hypoxia and neoangiogenesis on the growth of pancreatic cancer.
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DOI：
10.1186/1476-4598-2-12
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发表时间：
2003-01-22
期刊：
影响因子：
37.3
通讯作者：
Hines OJ
中科院分区：
文献类型：
--
作者：
Duffy JP;Eibl G;Reber HA;Hines OJ
与其他实体瘤一样，胰腺癌的生长和转移严重依赖于肿瘤血管生成。肿瘤募集额外血管的主要刺激是细胞缺氧，这种情况在这种肿瘤中尤其明显。缺氧诱导改变细胞代谢和促进新血管生成的基因的转录激活。胰腺癌细胞已经证明即使在缺氧的情况下也能激活这种适应性通路。这种肿瘤的高血管生成反应与肿瘤生长增加、转移增加和生存率降低相关。表达高水平的血管内皮生长因子（一种有效的促血管生成细胞因子）的胰腺癌也具有较高的转移发生率和较差的预后。胰腺癌细胞独特地表达血管内皮生长因子受体，表明自分泌环在肿瘤增殖和侵袭中的作用。多种实验性抗血管生成策略，其中许多以血管内皮生长因子为靶点，可减少胰腺癌的生长、扩散和血管生成。当作为联合化疗方案的组成部分时，胰腺癌的抗血管生成治疗可能是最有效的。
As with other solid tumors, the growth and metastasis of pancreatic cancer is critically dependent on tumor angiogenesis. A major stimulus for a tumor's recruitment of additional blood vessels is cellular hypoxia, a condition which is especially pronounced in this neoplasm. Hypoxia induces transcriptional activation of genes that alter cellular metabolism and promote neoangiogenesis. Pancreatic cancer cells have demonstrated activation of such adaptive pathways even in the absence of hypoxia. A highly-angiogenic response in this neoplasm correlates with increased tumor growth, increased metastasis, and decreased survival. Pancreatic cancers expressing high levels of vascular endothelial growth factor, a potent pro-angiogenic cytokine, also have a higher incidence of metastasis and poorer prognosis. Pancreatic cancer cells uniquely express receptors for vascular endothelial growth factor, indicating a role for an autocrine loop in tumor proliferation and invasion. Multiple experimental anti-angiogenic strategies, many of which target vascular endothelial growth factor, reduce pancreatic cancer growth, spread, and angiogenesis. Anti-angiogenic treatments for pancreatic cancer will likely be most effective when used as an integral part of a combination chemotherapeutic regimen.