title: Tumor-associated primo vascular system is derived from xenograft, not host.
abstract: The primo vascular system (PVS), which is composed of very small primo-vessels (PV) and primo-nodes (PN), has recently emerged as a third component of circulatory system. Here, we report the presence of a tumor derived PVS in murine xenografts of human histiocytic lymphoma (U937) in close proximity to the tumor. Within this system, PNs are small (~500-600 μM diameter) membranous sac-like structures which contain numerous small cells which can be demonstrated by DAPI staining. Hematoxylin and Eosin (H&E) staining of the peri-tumoral PVS shows the presence of loose structures lined by fibroblasts but filled with dense fibers, cells, lacunae and nerve-like structures. The origin and type of cells within the PVS was characterized by immunostaining with antibodies for CD68, CD45 and lysozyme. The results of these studies reveal that the PVS of the xenograft originates from the human U937 tumor cells. qRT-PCR analysis of mRNA isolated from PVS cells reveals a striking predominance of human, rather than mouse, sequences. Of particular interest, human stem cell specific transcription factors were overexpressed, most notably KLF4, an upstream regulator of NANOG which maintains the pluripotent and undifferentiated state of stem cells. These results suggest that the cells present within the PVS are derived from the human xenograft and suggests that the primo-vessels associated with the xenografted tumor may provide a safe haven for a select population of cancer stem cells. Further understanding of the biological properties of these cells may allow the development of new anti-cancer interventions.
authors.affiliation: Department of Medicine, University of Louisville, 505 S Hancock St., Louisville, KY 40202, USA. ashrafulislam01@gmail.com
authors.forename: Md Ashraful
authors.initials: MA
authors.lastname: Islam
authors.forename: Shelia D
authors.initials: SD
authors.lastname: Thomas
authors.forename: Kara J
authors.initials: KJ
authors.lastname: Sedoris
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Slone
authors.forename: Houda
authors.initials: H
authors.lastname: Alatassi
authors.forename: Donald M
authors.initials: DM
authors.lastname: Miller
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D045744:Cell Line, Tumor; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000276:immunology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology*; D016740:Meridians; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009113:Muramidase / Q000378:metabolism; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D055153:Stem Cell Niche; D014183:Transplantation, Heterologous; D020298:U937 Cells; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D017493:Leukocyte Common Antigens; D009113:Muramidase; D012333:RNA, Messenger; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse