Neuropeptides as cellular growth factors: role of multiple signalling pathways
Neuropeptides as cellular growth factors: role of multiple signalling pathways
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DOI：
10.1111/j.1365-2362.1991.tb01801.x
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发表时间：
1991-04
影响因子：
5.5
通讯作者：
E. Rozengurt
中科院分区：
文献类型：
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作者：
E. Rozengurt
在UIVO中，许多组织和器官的细胞保持在非增殖状态(Go/Gl)。然而，当暴露于激素、抗原或生长因子等外界刺激时，此类细胞仍可存活，并可被诱导恢复DNA合成和细胞分裂。以这种方式，个体细胞的生长是根据整个生物体的需要来调节的。这些有丝分裂原调节细胞生长的分子机制可能被证明对理解癌细胞的正常增殖反应和不受限制的生长至关重要。许多关于生长因子的研究都使用了培养的成纤维细胞，如小鼠3T3细胞，作为模型系统111。当这些细胞耗尽其促进生长的活性时，它们停止增殖，并可以通过补充新鲜血清，或者通过在无血清培养基中添加多肽生长因子或药物来刺激它们重新启动DNA合成和细胞分裂(图2)。I)。使用这种静止细胞和确定的生长因子组合进行的研究表明，存在有效和特定的协同作用信号转导通路，几乎是在丝裂原添加后立即启动的[L-31]。人们越来越认识到，小的调节肽在整个身体的细胞信息处理的复杂网络中扮演着分子信使的角色。它们可以作用于神经节后受体(神经递质)，作用于释放它们的同一细胞(自分泌机制)、相邻细胞(旁分泌通讯)或身体任何地方的远距离靶细胞或器官(内分泌激素)。这些多肽作为快速作用的神经体液信号传递者的经典作用最近受到了挑战，因为发现它们还能刺激细胞增殖(43)。特别是，蛙皮素、血管-
The cells of many tissues and organs in uivo are maintained in a non-proliferating state (Go/Gl). However, such cells remain viable and can be induced to resume DNA synthesis and cell division when exposed to external stimuli such as hormones, antigens or growth factors. In this manner the growth of individual cells is regulated according to the requirements of the whole organism. The e1ucidati:on of the molecular mechanism by which these mitogens regulate cellular growth may prove crucial to understanding both the normal proliferative response and the unrestrained growth of cancer cells. Many studies of growth factors have used cultured fibroblasts, such as murine 3T3 cells, as a model system 111. These cells cease to proliferate when they deplete the medium of its growth-promoting activity and can be stimulated to re-initiate DNA synthesis and cell division either by replenishing the medium with fresh serum, or by the addition of polypeptide growth factors or pharmacological agents in serum-free medium (Fig. I ) . Studies performed using such quiescent cells and defined combinations of growth factors have revealed the existence of potent and specific synergistically acting signal transduction pathways initiated almost immediately following mitogen addition [l-31. It is increasingly recognized that small regulatory peptides act as molecular messengers in a complex network of information processing by cells throughout the body. They may act on post-ganglionic receptors (neurotransmitters), on the same cells that released them (autocrine mechanism), adjacent cells (paracrine communication) or distant target cells or organs anywhere in the body (endocrine hormones). The classical role of these peptides as fast-acting neurohumoral signallers has recently been challenged by the discovery that they also stimulate cell proliferation (reviewed in 43). In particular, bombesin [6], vaso-