Disruption of Id1 reveals major differences in angiogenesis between transplanted and autochthonous tumors.
Id genes regulate tumor angiogenesis and loss of Id1 inhibits tumor xenograft growth in mice. Here we evaluate the role of Id1 in a more clinically relevant tumor model system using a two-step chemical carcinogenesis protocol. Remarkably, we find that Id1-/- mice are more susceptible to skin tumorigenesis compared to their wild-type counterparts. Cutaneous neoplasms in Id1-/- mice show increased proliferation without alterations in tumor angiogenesis; however, Id1-/- mice possess 50% fewer cutaneous gammadelta T cells than their wild-type counterparts due to an intrinsic migration defect associated with loss of expression of the chemokine receptor, CXCR4. We suggest that there are important differences between the mechanisms of angiogenesis in transplanted and autochthonous tumors and that these findings will have significant implications for the potential utility of antiangiogenic therapies in cancer.
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Hashmat
H
Sikder
David L
DL
Huso
Hong
H
Zhang
Binghe
B
Wang
Byungwoo
B
Ryu
Sam T
ST
Hwang
Jonathan D
JD
Powell
Rhoda M
RM
Alani
D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D004730:Endothelium, Vascular / Q000503:physiopathology; D005434:Flow Cytometry; D051798:Inhibitor of Differentiation Protein 1; D008545:Melanoma / Q000139:chemically induced / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D019718:Receptors, CXCR4 / Q000378:metabolism; D012097:Repressor Proteins; D012878:Skin Neoplasms / Q000139:chemically induced / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous
D002273:Carcinogens; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D019718:Receptors, CXCR4; D012097:Repressor Proteins; D014157:Transcription Factors