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

IGF 结合蛋白 3 (IGFBP-3) 对乳腺癌细胞生长的内分泌和自分泌调节。

• 批准号: nhmrc : 302153
• 负责人: Dr Janet Martin
• 金额: $ 33.16万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2004
• 资助国家: 澳大利亚
• 起止时间: 2004-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/endocrine-autocrine-regulation-igfbp-3/99206
• 关键词: Endocrine; autocrine; regulation; breast; cancer

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.

生长因子及其调节蛋白的胰岛素样生长因子（IGF）系统对于正常生长是必不可少的，但也涉及许多过度生长障碍。一些临床研究表明，血液中高水平的IGF-I会增加一些女性患乳腺癌的风险，但如果在循环中携带它的蛋白质IGFBP-3也很高，风险就会降低。因此，已经表明IGFBP-3可用于治疗乳腺癌。实验室研究表明IGFBP-3可以抑制细胞分裂并刺激许多细胞类型的细胞死亡，包括乳腺细胞。然而，一些细胞对IGFBP-3的抑制作用有抗性，并且在某些情况下IGFBP-3可以刺激细胞生长和分裂。事实上，乳腺肿瘤中IGFBP-3的含量在生长最快、最恶性的肿瘤中最高，这表明IGFBP-3可能刺激它们的生长。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与另一种参与快速组织生长的激素系统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一些重要的问题：IGFBP-3如何与EGF系统相互作用以刺激肿瘤生长;来自血液的IGFBP-3是否促进EGF敏感性肿瘤的生长;以及IGFBP-3与EGF系统之间的相互作用是否可以被废除，或从生长刺激转换为生长抑制，从而抑制肿瘤生长。阐明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的治疗过度生长障碍的新疗法。