Unlocking the mechanism of kallikreins modulating the adhesion of prostate cancer cells to bone

解开激肽释放酶调节前列腺癌细胞与骨粘附的机制

• 批准号: 166524083
• 负责人: Dr.-Ing. Anna Taubenberger
• 金额: --
• 依托单位: Biotechnologisches Zentrum (Biotec)
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/166524083?language=en
• 关键词: Unlocking; mechanism; kallikreins; modulating; adhesion

Members of the kallikrein family of serine proteases are strongly associated with prostate cancer. Preliminary experiments with prostate cancer cells expressing the kallikreins hK3 and hK4 suggest that hK3 and hK4 lead to EMT-like changes (EMT: epithelial to mesenchymal transformation) in these cells. Hence, it may be supposed that hK3 and hK4 are involved in the progression of localized prostate cancer to a metastatic stage. Since the development of prostate cancer metastases, mainly located in bone, results in poor prognosis for patients, it is of great importance to study the mechanisms that enable prostate tumor cells to adhere to the bone environment. To investigate if decreased E-cadherin levels upon hK3 and hK4 expression lead to decreased cell-cell adhesion, functional cell adhesion assays are needed. For that purpose single-cell force spectroscopy, an atomic force microscopy based approach, may be used. Besides cell-cell adhesion, adhesion of PC3 cells to matrices that mimic the bone ECM may be analyzed. These experiments will help to understand the molecular mechanisms by which tumor cells interact with the bone environment during the development of bone metastases. Complementary to the adhesion measurements, the link between kallikreins and adhesion molecule expression will be investigated using cell biological and biochemical analysis techniques.

丝氨酸蛋白酶的激肽释放酶家族的成员与前列腺癌密切相关。用表达激肽释放酶hK 3和hK 4的前列腺癌细胞进行的初步实验表明，hK 3和hK 4导致这些细胞中的EMT样变化（EMT：上皮向间充质转化）。因此，可以推测hK 3和hK 4参与了局限性前列腺癌向转移阶段的进展。由于前列腺癌转移的发展，主要位于骨中，导致患者预后不良，因此研究使前列腺肿瘤细胞粘附于骨环境的机制具有重要意义。为了研究hK 3和hK 4表达后E-钙粘蛋白水平的降低是否导致细胞-细胞粘附的降低，需要功能性细胞粘附测定。出于该目的，可以使用单细胞力光谱法，一种基于原子力显微镜的方法。除了细胞-细胞粘附之外，还可以分析PC 3细胞对模拟骨ECM的基质的粘附。这些实验将有助于了解肿瘤细胞在骨转移发展过程中与骨环境相互作用的分子机制。作为粘附测量的补充，将使用细胞生物学和生化分析技术研究激肽释放酶和粘附分子表达之间的联系。