Inflammation and the tumour microenvironment in breast cancer: The role of Stat3 and NF-kB

乳腺癌中的炎症和肿瘤微环境：Stat3 和 NF-kB 的作用

• 批准号: G0900980/1
• 负责人: Christine Watson
• 金额: $ 47.76万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0900980%2F1
• 关键词: Inflammation; tumour; microenvironment; breast; cancer

Breast cancer is a common disease in post-menopausal women. Although surgery and chemotherapy prolong life, many breast tumours spread to other organs and this metastatic disease causes the death of the patient. There is evidence from epidemiological studies that, although pregnancy can reduce the lifetime risk of breast cancer, women have a higher risk in the 5-10 years following a pregnancy. We propose that this risk is due to the factors that are present in the breast during the period immediately following lactation (involution), when the milk-producing cells die and secrete a number of inflammatory substances. Our studies on the processes that take place during involution have identified some of these factors. In this project, we propose to delete two signaling molecules that are key regulators of involution and measure the effect this has on tumour formation in models of breast cancer. Once we have identified the most important factors, we will compare levels of these in cell lines derived from breast cancer tissues. We will then specifically block these factors in breast cancer cells and measure how this affects their growth and spread in a novel tissue scaffold that we are developing to provide a 3-D model of the breast. It is hoped that this work will reveal new therapeutic targets or markers of breast cancer.

乳腺癌是绝经后妇女的常见病。虽然手术和化疗可以延长生命，但许多乳腺肿瘤扩散到其他器官，这种转移性疾病导致患者死亡。流行病学研究的证据表明，虽然怀孕可以减少乳腺癌的终生风险，但妇女在怀孕后5-10年内的风险较高。我们认为，这种风险是由于哺乳期（退化）后立即出现在乳房中的因素造成的，此时产奶细胞死亡并分泌大量炎症物质。我们对退化过程的研究已经确定了其中的一些因素。在这个项目中，我们建议删除两个信号分子，它们是退化的关键调节因子，并测量这对乳腺癌模型中肿瘤形成的影响。一旦我们确定了最重要的因素，我们将比较来自乳腺癌组织的细胞系中这些因素的水平。然后，我们将在乳腺癌细胞中特异性地阻断这些因子，并测量这如何影响它们在我们正在开发的新型组织支架中的生长和扩散，以提供乳腺的3D模型。希望这项工作将揭示乳腺癌新的治疗靶点或标志物。