Abstract

Abstract The ability of cancer cells especially immature and multi-potent cancer stem cells to escape from conventional therapeutic intervention has been long investigated. The exact mechanisms and safe harboring of this population of cells have yet to be identified. The primo vascular system (PVS) which is composed of new types of micro-conduits named primo-vessels (PV) and primo-nodes (PN) has recently emerged as a third component of circulatory system. In this study, we have shown the existence of PVS and their networks in murine xenograft of human histiocytic lymphoma cells (U937) using trypan blue. These PVs are thread-like, elastic, multi-lumen structure and appears to radiate from PN, perpendicular of the conventional venuoles-arteriols and reside in close proximity to the tumor. PNs are about 500-600 μM membranous sac-like structures, containing numerous tiny cells evident by DAPI staining. Isolation of RNA from PVS signifies the presence of intact transcriptional machinery in the cells. Hematoxylin and Eosin (H&E) staining of PVS shows the presence of loose and abortive structure lined by fibroblast but filled with lightly dense fibers, cells, lacuna and nerve-like structures. To further characterize the origin and type of cells within the PVS, immunostaining with antibodies for CD68, CD45 and lysozyme has revealed the cells are same immunophenotype as of U937. RT-PCR arrays demonstrates a hundred to thousand fold up regulation of human cancer stem cell specific transcription factors most notably KLF4, an upstream regulator of NANOG which maintain the pluripotent and undifferentiated state of stem cells. These results suggest that PVS close to the tumor could be the safe haven for a selective population of cancer stem cell. Further understanding of the biological properties and responsiveness to therapy of these cells will shed light on new dimensions of anti-cancer interventions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5193. doi:1538-7445.AM2012-5193

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