Transplanted bone marrow cells preferentially home to the vessels of in situ generated murine tumors rather than of normal organs.
Transplanted bone marrow-derived (BM) cells have been shown to home into the tumor vessels of s.c. implanted tumor models and to functionally contribute to tumor neoangiogenesis and tumor growth. However, whether BM cells contribute to the vessels of in situ developing tumors remains unknown. We have taken advantage of the in situ generation of mammary tumors in transgenic mice carrying the polyoma virus middle T oncogene (MMTV-PyVT) to determine whether transplanted BM cells home to and incorporate into the intratumoral vessels. Unfractionated BM from lacZ+ROSA 26 mice was used to rescue irradiated MMTV-PyVT transgenic mice or their wild-type congenics. All transgenic mice were sacrificed when they developed easily palpable mammary tumors. BM cells recruited and incorporated into the vasculature were identified by coexpression of lacZ and CD31, evidence that these cells had a distinctive, elongated appearance and that they lined the vessel structures. We found that BM cells home to and incorporate into 1.3% of the vessels of all in situ generated mammary adenocarcinomas examined (n=8). In contrast, BM cells did not recruit into the vessels of colon or liver of the tumor-bearing mice. Whether these cells contribute to new vessel formation via vasculogenesis or angiogenesis or simply attach to, and integrate into, the growing tips or shafts of pre-existing vessels has to be determined. BM could be used as a vehicle for the specific transport of antiangiogenic signals into the tumor vascular bed.
Dwenger
Anne
A
Department of Hematology/Oncology, Freiburg University Medical Center, Freiburg, Germany.
Rosenthal
Felicia
F
Machein
Márcia
M
Waller
Cornelius
C
Spyridonidis
Alexandros
A
D000818:Animals; D001808:Blood Vessels / Q000254:growth & development* / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D042783:Endothelial Cells / Q000473:pathology / Q000502:physiology; D005822:Genetic Vectors / Q000235:genetics; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000473:pathology / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D009857:Oncogenes / Q000235:genetics; D011120:Polyomavirus / Q000235:genetics; D014162:Transfection / Q000379:methods; D019076:Transgenes / Q000235:genetics