For this reason, we investigated the role of EGFL7 expression in the metastatic progression of the HT1080 cell line in vitro and in vivo. We found that over-expression of EGFL7 in HT1080 cells does not affect their proliferation in vitro. In an in vivo chorioallantoic membrane angiogenesis assay, over-expression of EGFL7 significantly reduced angiogenesis compared to controls. When tumors were grown in an avian xenograft PF477736 model, those expressing high levels of EGFL7 grew more slowly and showed significantly delayed vascularization. Analysis of the vascular ultrastructure suggested
that the vasculature in EGFL7 over-expressing tumors was less tortuous and leaky compared to controls. Metastasis of HT1080 cells to the brain and liver was reduced by more than 80% in EGFL7 over-expressing
tumors. Taken together, these buy Eltanexor results indicate that expression of EGFL7 by tumors influences the stability of the neovasculature and therefore, it may be a novel therapeutic target for anti-cancer strategies. O171 A Novel Role for Megakaryocytes in the Bone Marrow Microenvironment of Prostate Cancer Metastasis Xin Li1, Serk In Park1, Amy Koh1, Ken Pienta2,4, Laurie McCauley 1,3 1 Periodontics & Oral Medicine, University of Michigan, Ann Arbor, MI, USA, 2 Urology, University of Michigan, Ann Arbor, MI, USA, 3 Pathology, University of Michigan, Ann Arbor, MI, USA, 4 Internal Medicine, University of Michigan, Ann Arbor, MI, USA Bone marrow
is an accommodating microenvironment Bafilomycin A1 concentration for prostate cancer cell localization and growth; however, host countermeasures likely exist to constrain tumor occupation of the skeleton. Megakaryocytes develop adjacent to bone and migrate to the vascular sinusoids before releasing platelets to the circulation. Hence, they have the potential to encounter tumor cells early in their progression into the bone. The purpose of this study was to determine the impact of megakaryocytes triclocarban (MKs) on prostate cancer (PCa) cells using in vitro and in vivo approaches. K562 (human megakaryocyte precursors) and primary MKs induced from mouse bone marrow hematopoietic precursor cells were used in co-culture experiments with PCa cells (PC-3, VCaP, C4-2B). K562 potently suppressed PC-3, VCaP, and C4-2B cell numbers in co-culture; whereas they increased osteoblastic SaOS2 cells. The MK/PCa restrictive effect was more potent when cells were cultured in direct contact, and also when less differentiated MKs were used. The inhibitory effect of MKs was pro-apoptotic as determined by propidium iodide (PI) and annexin V flow cytometric analysis in addition to a restrictive proliferative effect seen via reduced levels of cyclin D1 mRNA.