Ⅳ型胶原在癌侵袭转移过程中的动态变化:脉冲模式  

Dynamic Changes of Collagen Ⅳ During Cancer Invasion and Migration: Pulse Mode

作　　者：方敏[1] 袁静萍[1] 彭春伟[1] 刘少平[1] 李雁[1] 

机构地区：[1]武汉大学中南医院肿瘤科,肿瘤生物学行为湖北省重点实验室,湖北省肿瘤医学临床研究中心,武汉430071

出　　处：《生物化学与生物物理进展》2013年第10期1056-1062,共7页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(81230031/H18;81171396);国家科技重大专项(2012ZX10002012-12);国家大学生创新训练计划项目(111048673)资助~~

摘　　要：结合量子点原位分子成像技术探究了基于Ⅳ型胶原动态改变的癌侵袭转移模式.收集肝癌、胃癌、乳腺癌和宫颈癌的临床病理标本,利用免疫组化和量子点成像技术对癌细胞及其相关微环境中的关键分子进行成像,观察癌侵袭转移过程中Ⅳ型胶原的动态变化.结果表明,在癌侵袭和转移过程中Ⅳ型胶原呈现动态改变.首先在基底膜处交联增多,形成不规则且致密的袖套包裹癌巢;随后多处基底膜处的胶原发生构象改变并被降解形成侵袭前锋.同时,伴随着间质中的Ⅳ型胶原重新线性沉积及巨噬细胞的团聚增多,癌细胞最终逃逸转移.由上述结果可以断定,癌侵袭转移呈现"脉冲模式",Ⅳ型胶原的动态改变为癌侵袭转移创造了适宜的微环境.Cancer invasion and metastasis remain two root causes of mortality. This process involves alterations of tumor microenvironment, particularly the remodeling of extracellular matrix（ECM）, characterized by collagen Ⅳ uncoiling, degradation, fragments deposition and cross-linking. This study was aimed to reveal the cancer invasion mode based on dynamic changes of collagen Ⅳ by novel quantum dots （QDs） imaging technology. Cancer tissues of hepatocellular carcinoma, gastric cancer, breast cancer and cervical carcinoma were collected and stained by traditional immunohistochemistry and novel QDs-based imaging technology. Several key molecules representing of cancer cells and tumor microenvironment were studied, including Ki67, representing of proliferation of cancer cells, macrophages, representing of monocytes infiltration and collagen Ⅳ, representing of tumor stroma remodeling during cancer invasion and migration. During cancer invasion and migration, collagen Ⅳ had structural and functional changes. In different cancer tissues, 4 types of collagen Ⅳ could be observed, consisting of linear, irregular, fragmented and disappeared. However, several common features were evident during the dynamic process of cancer progression. First, collagen Ⅳ at basement membrane increased, presenting an irregular sheath surrounding cancer nests; then, collagen Ⅳ was degraded to form invasion fronts at several sites accompanied with linear re-deposition of collagen Ⅳ and increased macrophages in ECM. Second, cancer cells escaped from large cancer nests to seed in ECM. And also the dynamic changes of collagen Ⅳ were accompanied with the recruitment of macrophages, together to regulate and affect biological behaviors of cancer cells. A series changes caused by dynamic changes of collagen Ⅳ provide a proper tumor microenvironment for cancer invasion and migration. In this dysfunctional tumor microenvironment, tumor mass becomes increasingly harder with tumor stroma stiffening causing high ECM stress. With cancer

关 键 词：癌 Ⅳ型胶原 细胞外间质重塑 量子点 

分 类 号：R73-37[医药卫生—肿瘤]