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Updated: May 18, 2026
A Patient-Derived Xenograft Model for Venous Malformation
Published on: June 15, 2020
Tumor-associated primo vascular system is derived from xenograft, not host
Md Ashraful Islam1, Shelia D Thomas, Kara J Sedoris
1Department of Medicine, University of Louisville, 505 S Hancock St., Louisville, KY 40202, USA. ashrafulislam01@gmail.com
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.
Insights
Researchers discovered a tumor-derived primo vascular system (PVS) in lymphoma xenografts. This PVS contains human cancer stem cells, suggesting it may act as a protective niche and offering potential new anti-cancer intervention targets.
Area of Science:
- Vascular Biology
- Cancer Stem Cell Research
- Tumor Microenvironment
Background:
- The primo vascular system (PVS), a potential third circulatory system, comprises primo-vessels (PV) and primo-nodes (PN).
- Its role in tumor biology remains largely unexplored.
- Understanding novel vascular structures in tumors is crucial for therapeutic development.
Purpose of the Study:
- To investigate the presence and origin of a PVS associated with human histiocytic lymphoma (U937) xenografts in mice.
- To characterize the cellular components and potential function of this tumor-derived PVS.
- To explore the implications for cancer stem cell survival and potential therapeutic strategies.
Main Methods:
- Xenograft model using human U937 lymphoma cells in mice.
- Histological analysis using Hematoxylin and Eosin (H&E) staining.
- Immunostaining for cell markers (CD68, CD45, lysozyme) and DAPI staining for nuclei.
- Quantitative reverse transcription PCR (qRT-PCR) to analyze gene expression (human vs. mouse sequences, stem cell factors KLF4, NANOG).
Main Results:
- A tumor-derived PVS, including primo-nodes (PNs), was identified adjacent to U937 lymphoma xenografts.
- PNs contained numerous cells, and histological analysis revealed complex structures within the PVS.
- Immunostaining and qRT-PCR confirmed that PVS cells originated from the human U937 tumor, not the mouse host.
- Overexpression of human stem cell transcription factors, including KLF4, was observed in PVS cells.
Conclusions:
- The primo vascular system associated with U937 lymphoma xenografts is derived from human tumor cells.
- The PVS may serve as a sanctuary or niche for cancer stem cells within the tumor microenvironment.
- These findings suggest novel therapeutic targets for anti-cancer interventions by targeting this specialized vascular system.
