期刊
CANCER LETTERS
卷 381, 期 1, 页码 252-258出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2015.12.027
关键词
Pancreatic cancer; Fibronectin; Extracellular matrix; Chemoresistance; Metastasis; Integrin
类别
资金
- American Cancer Society (ACS) [RSG-10-244-01-CSM]
- Joe and Jessie Crump Medical Research Foundation
- NIH [T32 GM008203]
- Effie Marie Cain Scholarship in Angiogenesis Research
Pancreatic ductal adenocarcinoma (PDA) is a highly metastatic disease that resists most current therapies. A defining characteristic of PDA is an intense fibrotic response that promotes tumor cell invasion and chemoresistance. Efforts to understand the complex relationship between the tumor and its extra cellular network and to therapeutically perturb tumor-stroma interactions are ongoing. Fibronectin (FN), a provisional matrix protein abundant in PDA stroma but not normal tissues, supports metastatic spread and chemoresistance of this deadly disease. FN also supports angiogenesis, which is required for even hypovascular tumors such as PDA to develop and progress. Targeting components of the tumor stroma, such as FN, can effectively reduce tumor growth and spread while also enhancing delivery of chemotherapy. Here, we review the molecular mechanisms by which FN drives angiogenesis, metastasis and chemoresistance in PDA. In light of these new findings, we also discuss therapeutic strategies to inhibit FN signaling. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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