Our data pointed to L1 also as a marker of certain hematopoietic cell lineages. The functional relevance of these observations was tested in a conditional knockout mouse model, which revealed the causal role of L1 in the transendothelial migration of immune cells and in their trafficking in vivo, two processes strictly related to cancer progression. Hence, L1 is present in invasive tumor cells, in cancer-associated vasculature and in inflammatory cells, and in all these cell types its function is consistent with a pro-malignant role through the modulation AMN-107 order of tumor-host

interactions. These observations provide the rationale to explore L1 targeting as a strategy to interfere with the tumor-promoting action of some microenvironment components. O65 Further Defining Reactive Stroma in Prostate Cancer David Barron 1 , Douglas Strand2, Isaiah Schauer3, Steven Ressler1, Truong Dang1, David Rowley1 1 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA, 2 Vanderbilt Prostate Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA, 3 Department of Pathology,

MD Anderson Cancer Center, Houston, TX, USA Myofibroblasts make up reactive stroma associated with prostate, mammary, lung, colon, and stomach carcinoma, suggesting that this cell type plays a critical role in a generalized response to injury. Our lab has shown a direct correlation of degree of reactive stroma with both severity and HDAC inhibitor biochemical recurrence of human prostate cancer. The precise origin Epigenetics inhibitor of myofibroblasts and their mechanism of recruitment in cancer are unknown. Recent studies in wound repair suggest that at sites of reactive stroma they originate

from fibrocytes derived from circulating CD34+ hematopoietic progenitor cells. TGF-β has emerged as a key factor in mediating the recruitment and differentiation of fibrocytes to sites of wounding, however its corresponding role in cancer has not been examined. To further understand the role of reactive stroma in adenocarcinoma, Acyl CoA dehydrogenase we analyzed several tissue microarrays containing patient matched normal and cancer regions that were subjected to a dual labeling immunohistochemistry approach. Recent data suggest that prostate cancer reactive stroma originates from vimentin+/CD34+/CD14+ progenitor cells that are juxtaposed to the sub-basal lamina surface at the stromal-epithelial junction. Moreover, xenograft modeling studies suggest that reactive stroma originates from bone marrow derived cells that may be of the monocyte series. Mechanistic studies examining TGF-β overexpression in vivo demonstrate age-dependent changes that mimic human reactive stroma. Transgenic mice exhibited focal collagenous micronodules that appear to correlated with TGF-β1 expression. Intraluminal fibroplasia with influx of inflammatory cells was also present in various regions of transgenic prostate.