M. S. Hu1, Z. Maan1, W. Hong1, G. Walmsley1, R. Rennert1, T. Zhu1, M. Esquivel1, D. Atashroo1, D. Duscher1, R. Tevlin1, A. Zimmermann1, M. Chung1, A. McArdle1, G. Gurtner1, H. P. Lorenz1, A. Giaccia3, M. Longaker1 1Stanford University,Surgery,Palo Alto, CA, USA 2University Of Hawaii,Surgery,Honolulu, HI, USA 3Stanford University,Radiation Oncology,Palo Alto, CA, USA
Introduction:
Tumors have been described as wounds that do not heal based upon similarities in stromal composition, angiogenesis, and gene expression. However, the interactions between the two processes have yet to be clearly examined. We previously developed a novel in vivo tumor wound competition model to examine the interactions between wound healing and tumor growth. Prior studies demonstrate that the placement of a full thickness excisional wound will inhibit tumor growth as the wound is healing. Herein, we study the role of circulating progenitor/stem cells in this phenomenon.
Methods:
Parabiosis was performed with NOD-SCID-gamma (NSG) and NSG-GFP mice. After cross circulation was confirmed at 2 weeks, head and neck squamous cell carcinoma (HNSCC) SAS cells were injected subcutaneously and a splinted full thickness excisional wound was created on the dorsum of the NSG parabiont. After 10 days, the tumor and wound were harvested, digested, and analyzed via fluorescence-activated cell sorting.
Results:
Identification of circulating cells by GFP fluorescence show wounds recruit more circulating cells than tumors (8.63% vs. 3.9%; *p<0.05). Furthermore, progenitor cells (GFP+ Lin-) had better recruitment by wounds versus tumors (0.7% and 0.28%; *p<0.05). Using subset analysis, the ability of wounds to recruit hematopoietic progenitor cells (GFP+ Lin- c-Kit+) and putative endothelial cells (GFP+ Lin- VEGFR2+) were demonstrated (13.1% vs. 4.01%; p<0.05 and 7.24% vs. 3.11% ; p<0.05, respectively).
Conclusion:
We conclude that wounds recruit more circulating progenitor cells than tumors using a parabiosis model. This may explain how wounds can inhibit tumor growth when placed adjacently in vivo. With further studies, insight into this mechanism may offer a deeper understanding of both tumor growth and wound healing.