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Among various tumors, pancreatic ductal adenocarcinoma (PDAC) typically develops in an unusually disordered microenvironment, which contributes to its highly aggressive behavior. Since anti\u2010vascular endothelial growth factor (VEGF) (Avastin) has failed to demonstrate a survival benefit in PDAC, we need to re\u2010visit the basic biology of this disease and understand what makes it so refractory to the anti\u2010angiogenic approaches that are clinically effective in other neoplasms. To address this issue, we specifically focused on the process of neovascularization where bone marrow\u2010derived cells (BMDCs) play a role during pancreatic tumorigenesis. We have identified subsets of BMDCs that regulate key processes during development of the neovessels through paracrine Hedgehog signaling. Considering the importance of systemic responses occurring in tumor bearing hosts, we are currently using genetically engineered mice, which spontaneously develop PDAC, Pdx1\u2010Cre;LSL\u2010Kras<jats:sup>G12D<\/jats:sup>;p53<jats:sup>lox\/+<\/jats:sup> strain, to clarify critical events that can trigger aberrant angiogenesis in pancreatic cancer. These studies allow us to provide insights into the cellular and molecular mechanisms of pancreatic tumorigenesis and have an implication for the design of therapies against this difficult disease.<\/jats:p>","DOI":"10.1111\/j.1440-1746.2011.07012.x","type":"journal-article","created":{"date-parts":[[2012,2,9]],"date-time":"2012-02-09T16:17:21Z","timestamp":1328804241000},"page":"23-26","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Bone marrow\u2010derived proangiogenic cells in pancreatic cancer"],"prefix":"10.1111","volume":"27","author":[{"given":"Yusuke","family":"Mizukami","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,2,9]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006676-200404000-00002"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.3322\/CA.2007.0010"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1997.15.6.2403"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.07.9525"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.01.185"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1259\/bjr\/16642775"},{"key":"e_1_2_8_8_2","first-page":"239","article-title":"Neovascularization in pancreatic ductal adenocarcinoma: microvessel count analysis, comparison with non\u2010cancerous regions and other types of carcinomas","volume":"9","author":"Ueda T","year":"2002","journal-title":"Oncol. 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