Hair follicle-derived blood vessels vascularize tumors in skin and are inhibited by Doxorubicin.
We have recently shown that the neural-stem cell marker nestin is expressed in hair follicle stem cells and the blood vessel network interconnecting hair follicles in the skin of transgenic mice with nestin regulatory element-driven green fluorescent protein (ND-GFP). The hair follicles were shown to give rise to the nestin-expressing blood vessels in the skin. In the present study, we visualized tumor angiogenesis by dual-color fluorescence imaging in ND-GFP transgenic mice after transplantation of the murine melanoma cell line B16F10 expressing red fluorescent protein. ND-GFP was highly expressed in proliferating endothelial cells and nascent blood vessels in the growing tumor. Results of immunohistochemical staining showed that the blood vessel-specific antigen CD31 was expressed in ND-GFP-expressing nascent blood vessels. ND-GFP expression was diminished in the vessels with increased blood flow. Progressive angiogenesis during tumor growth was readily visualized during tumor growth by GFP expression. Doxorubicin inhibited the nascent tumor angiogenesis as well as tumor growth in the ND-GFP mice transplanted with B16F10-RFP. This model is useful for direct visualization of tumor angiogenesis and evaluation of angiogenic inhibitors.
Amoh
Yasuyuki
Y
AntiCancer, Inc., San Diego, CA 92111-3604, USA.
Li
Lingna
L
Yang
Meng
M
Jiang
Ping
P
Moossa
Abdool R
AR
Katsuoka
Kensei
K
Hoffman
Robert M
RM
D000818:Animals; D048708:Cell Growth Processes / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018859:Hair Follicle / Q000098:blood supply*; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000188:drug therapy; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000098:blood supply* / Q000188:drug therapy
D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D004317:Doxorubicin