Biophysical Tools for the Characterization of Breast Cancer Cell Migration and Invasion

九分之一的加拿大妇女在其一生中会患上乳腺癌。死亡的原因不太可能是由于原发性乳腺肿瘤，而是由于癌症扩散到远处器官，这一过程称为转移。尽管在治疗方面取得了重大进展，但能够扩散到其他组织的乳腺癌在很大程度上仍然无法治愈。为了发现新的治疗靶点，需要更清楚地了解控制乳腺癌细胞在原发肿瘤和远处转移部位迁移和侵袭的机制。癌细胞的迁移和侵入部分地受到周围组织施加在癌细胞上的力的控制。然而，癌细胞必须将这些力量转化为改变细胞行为的结构或化学信号。需要成像工具来帮助破译这些力如何转化为细胞内的结构或化学变化。在这里，我们建议开发一个包含协议、成像条件、分析算法和软件包的完整工具箱，以控制并同时测量施加在细胞上的力和产生的细胞信号。协调力和信号度量将使我们能够理解这些过程是如何相互关联的，并开始理解控制乳腺癌转移的复杂机制。我们将开发越来越复杂的细胞模型系统，从1D发展到3D，以更接近生物环境。我们将与主要的企业合作伙伴一起将我们的软件商业化，并开发一个全面的培训计划，以确保癌症生物学和其他领域的研究人员能够有效地使用我们创建的工具箱。

One in nine Canadian women will develop breast cancer during their lifetime. The cause of death will not likely be due to theprimary breast tumor but due to the spread of the cancer to distant organs, a process known as metastasis. Despitesignificant advancements in treatments, breast cancers capable of spreading to other tissues remain largely incurable. Aclearer understanding of the mechanisms that control breast cancer cell migration and invasion within the primary tumor andat distant metastatic sites is needed in order to identify new and novel therapeutic targets. Cancer cell migration andinvasion is controlled, in part, by forces exerted upon cancer cells by surrounding tissue. However, the cancer cells mustconvert these forces into structural or chemical signals that alter cellular behavior. There is a need for imaging tools to helpdecipher how these forces are converted to structural or chemical changes within the cell. Here, we propose to develop acomprehensive toolbox of protocols, imaging conditions, analysis algorithms and software packages to control andsimultaneously measure forces applied to the cell and the cellular signals that result. Co-ordinating force and signalingmetrics will allow us to understand how these processes are inter-related and begin to comprehend the complexmechanisms controlling breast cancer metastasis. We will develop cellular model systems of increasing complexity,progressing from 1D to 3D, to more closely resemble the biological environment. We will commercialize aspects of oursoftware with major corporate partners and develop a comprehensive training program to ensure researchers across cancerbiology and other fields can effectively use the toolbox we create.