Endocrine and autocrine regulation of breast cancer cell growth by IGF binding protein-3 (IGFBP-3).

生长因子的胰岛素样生长因子（IGF）系统及其调节蛋白对正常生长至关重要，但也与许多过度生长疾病有关。一些临床研究表明，血液中高水平的igf - 1会增加一些女性患乳腺癌的风险，但如果在血液循环中携带igf - 1的蛋白质IGFBP-3也很高，风险就会降低。因此，有人建议IGFBP-3可能对乳腺癌的治疗有用。实验室研究表明，IGFBP-3可以抑制包括乳腺细胞在内的许多细胞类型的细胞分裂和刺激细胞死亡。然而，有些细胞对IGFBP-3的抑制作用有抵抗性，在某些情况下，IGFBP-3可能会刺激细胞生长和分裂。事实上，在生长最快的恶性肿瘤中，乳腺肿瘤中IGFBP-3的含量最高，这表明IGFBP-3可能刺激了它们的生长。我们的实验室数据表明，产生高水平IGFBP-3的乳腺癌细胞比产生很少或不产生IGFBP-3的细胞生长得更快。我们认为这是因为IGFBP-3与另一种参与组织快速生长的激素系统EGF系统相互作用，并增加其刺激乳腺细胞分裂的能力。这些观察结果提出了许多重要的问题：IGFBP-3如何与EGF系统相互作用以刺激肿瘤生长；血液中的IGFBP-3是否促进了egf敏感肿瘤的生长？IGFBP-3与EGF系统之间的相互作用是否可以被取消，或者从促进生长转变为抑制生长，从而抑制肿瘤生长。回答这些问题将提供关于IGFBP-3的刺激和抑制作用以及内分泌IGFBP-3在肿瘤生长中的作用的重要新信息，并有可能导致开发涉及IGFBP-3的治疗过度生长疾病的新疗法。

The insulin-like growth factor (IGF) system of growth factors and their regulatory proteins is essential for normal growth, but is also involved in a number of overgrowth disorders. Some clinical studies have shown that a high level of IGF-I in the blood increases the risk of breast cancer in some women, but if the protein which carries it in the circulation, IGFBP-3, is also high, the risk is reduced. It has therefore been suggested that IGFBP-3 may be useful in the treatment of breast cancer. This is supported by laboratory studies showing that IGFBP-3 can inhibit cell division and stimulate cell death in many cell types, including breast cells. However, some cells are resistant to IGFBP-3 s inhibitory effects, and in some cases IGFBP-3 may stimulate cells to grow and divide. In fact, the amount of IGFBP-3 present in breast tumours is highest in the fastest growing, most malignant tumours, suggesting that IGFBP-3 may be stimulating their growth. Our laboratory data indicates that breast cancer cells which produce a high level of IGFBP-3 grow faster as tumours than cells which produce little or no IGFBP-3. We believe that this is because IGFBP-3 interacts with another hormone system which is involved in rapid tissue growth, the EGF system, and increases its ability to stimulate breast cells to divide. These observations raise a number of important questions: how does IGFBP-3 interact with the EGF system to stimulate tumour growth; does IGFBP-3 from the blood promote the growth of EGF-sensitive tumours; and can the interaction between IGFBP-3 and the EGF system be abolished, or switched from growth stimulatory to growth inhibitory, thus inhibiting tumour growth. Answering these questions will provide important new information regarding IGFBP-3 s stimulatory and inhibitory actions, and the role of endocrine IGFBP-3 in tumour growth, and have the potential to lead to the development of novel therapies involving IGFBP-3 for the treatment of overgrowth disorders.