Sympathetic Neurotransmitters and Tumor Angiogenesis-Link between Stress and Cancer Progression.
Sympathetic Neurotransmitters and Tumor Angiogenesis-Link between Stress and Cancer Progression.
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DOI：
10.1155/2010/539706
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发表时间：
2010
影响因子：
--
通讯作者：
Kitlinska J
中科院分区：
文献类型：
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作者：
Tilan J;Kitlinska J
最近的证据支持一个长期存在的假设，即慢性应激可以影响肿瘤的生长和进展。研究表明，交感神经递质，如儿茶酚胺和神经肽，可以影响癌细胞生长和肿瘤血管形成。根据神经递质和肿瘤的类型，这些作用可以是刺激性和抑制性的。去甲肾上腺素（NE）和肾上腺素（E）是血管形成的有效刺激物，通过诱导肿瘤细胞释放血管生成因子和直接作用于内皮细胞（EC）功能两者起作用。因此，肾上腺素能系统的激活增加了各种类型肿瘤的生长，并已被证明介导了肿瘤进展的应激诱导的增强。另一方面，多巴胺（DA）干扰内皮细胞中的VEGF信号传导，阻断其血管生成功能并抑制肿瘤生长。另一种与NE共释放的交感神经递质神经肽Y（neuropeptide Y，NPY）直接刺激血管生成。然而，NPY的促血管生成作用可以通过其对肿瘤细胞增殖和存活的直接作用而改变。因此，NPY可以刺激或抑制肿瘤生长，这取决于肿瘤类型。因此，交感神经递质是肿瘤生长的强大调节剂，并可能成为癌症治疗的新靶点。
Recent evidence supports a longstanding hypothesis that chronic stress can influence tumor growth and progression. It has been shown that sympathetic neurotransmitters, such as catecholamines and neuropeptides, can affect both cancer cell growth and tumor vascularization. Depending on neurotransmitter and type of tumor, these effects can be both stimulatory and inhibitory. Norepinephrine (NE) and epinephrine (E) are potent stimulators of vascularization, acting both by inducing the release of angiogenic factors from tumor cells and directly on endothelial cell (EC) functions. As a result, activation of the adrenergic system increases growth of various types of tumors and has been shown to mediate stress-induced augmentation of tumor progression. Dopamine (DA), on the other hand, interferes with VEGF signaling in endothelial cells, blocks its angiogenic functions and inhibits tumor growth. Another sympathetic neurotransmitter coreleased with NE, neuropeptide Y (NPY), directly stimulates angiogenesis. However, proangiogenic actions of NPY can be altered by its direct effect on tumor cell proliferation and survival. In consequence, NPY can either stimulate or inhibit tumor growth, depending on tumor type. Hence, sympathetic neurotransmitters are powerful modulators of tumor growth and can become new targets in cancer therapy.