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

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，但许多乳腺肿瘤会扩散到其他器官，这种转移性疾病会导致患者死亡。流行病学研究的证据表明，虽然怀孕可以降低乳腺癌的终生风险，但妇女在怀孕后5-10年内的风险更高。我们认为，这种风险是由于乳房在哺乳(退缩)后的一段时间内存在的因素，此时产奶细胞死亡并分泌许多炎性物质。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，这两个分子是退化的关键调节因素，并在乳腺癌模型中测量这对肿瘤形成的影响。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，我们将专门在乳腺癌细胞中阻断这些因素，并测量这如何影响它们在一种新的组织支架中的生长和扩散，我们正在开发这种支架，以提供乳房的三维模型。人们希望这项工作将揭示乳腺癌的新治疗靶点或标记物。

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.