remodeling of tumor stroma and response to therapy重构的肿瘤基质和对治疗的反应.pdfVIP

Cancers 2012, 4, 340-353; doi:10.3390/cancers4020340 OPEN ACCESS cancers ISSN 2072-6694 /journal/cancers Review Remodeling of Tumor Stroma and Response to Therapy Anna Johansson and Ruth Ganss * Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, Perth 6000, Australia; E-Mail: ajohansson@.au * Author to whom correspondence should be addressed; E-Mail: ganss@.au; Tel.: +61-8-9224-0354; Fax: +61-8-9224-0322. Received: 24 February 2012; in revised form: 20 March 2012 / Accepted: 22 March 2012 / Published: 27 March 2012 Abstract: Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or en