Differential transplantability of tumor-associated stromal cells.
At the time of transplantation, tumor fragments contain "passenger" cells: endothelial cells and other stromal cells from the original host. Here, we investigated the fate of genetically labeled endothelial and nonendothelial stromal cells after transplantation in syngeneic mice. We report that angiogenic stroma associated with tumor or adipose tissue persists when transplanted, remains functional, and governs the initial neovascularization of grafted tissue fragments for more than 4 weeks after implantation. Surprisingly, the passenger endothelial cells survive longer than other stromal cells, which are replaced by host-activated fibroblasts after 3 weeks. The transplantability of tumor stroma suggests that the angiogenic potential of a tumor xenograft, which determines its viability, depends on the presence of passenger endothelial cells and other stromal cells within the xenograft. These studies of tumor tissue transplantation provide a platform for exploring the role of epithelial-stromal interactions in studies of tumor heterogeneity and drug resistance.
Duda
Dan G
DG
E. L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Fukumura
Dai
D
Munn
Lance L
LL
Booth
Michael F
MF
Brown
Edward B
EB
Huang
Peigen
P
Seed
Brian
B
Jain
Rakesh K
RK
D000818:Animals; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D042461:Vascular Endothelial Growth Factor A