Rothberg Jennifer M, Sameni Mansoureh, Moin Kamiar, Sloane Bonnie F
Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
Biochim Biophys Acta. 2012 Jan;1824(1):123-32. doi: 10.1016/j.bbapap.2011.07.025. Epub 2011 Aug 5.
Our laboratory has had a longstanding interest in how the interactions between tumors and their microenvironment affect malignant progression. Recently, we have focused on defining the proteolytic pathways that function in the transition of breast cancer from the pre-invasive lesions of ductal carcinoma in situ (DCIS) to invasive ductal carcinomas (IDCs). We use live-cell imaging to visualize, localize and quantify proteolysis as it occurs in real-time and thereby have established roles for lysosomal cysteine proteases both pericellularly and intracellularly in tumor proteolysis. To facilitate these studies, we have developed and optimized 3D organotypic co-culture models that recapitulate the in vivo interactions of mammary epithelial cells or tumor cells with stromal and inflammatory cells. Here we will discuss the background that led to our present studies as well as the techniques and models that we employ. This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome.
我们实验室长期以来一直关注肿瘤与其微环境之间的相互作用如何影响恶性进展。最近，我们专注于确定在乳腺癌从原位导管癌（DCIS）的侵袭前病变转变为浸润性导管癌（IDC）过程中起作用的蛋白水解途径。我们使用活细胞成像来实时可视化、定位和定量蛋白水解，从而确定了溶酶体半胱氨酸蛋白酶在肿瘤蛋白水解过程中在细胞周围和细胞内的作用。为了促进这些研究，我们开发并优化了三维器官型共培养模型，该模型概括了乳腺上皮细胞或肿瘤细胞与基质细胞和炎性细胞之间的体内相互作用。在这里，我们将讨论促成我们目前研究的背景以及我们所采用的技术和模型。本文是名为：溶酶体发现50年后的蛋白水解的特刊的一部分。
