Direct test of potential roles of EIIIA and EIIIB alternatively spliced segments of fibronectin in physiological and tumor angiogenesis.
Fibronectin splice variants containing the EIIIA and/or EIIIB exons are prominently expressed in the vasculature of a variety of human tumors but not in normal adult tissues. To understand the functions of these splice variants in physiological and tumor angiogenesis, we used EIIIB-null and EIIIA-null strains of mice to examine neovascularization of mouse retinas, pancreatic tumors in Rip-Tag transgenic mice, and transplanted melanomas. Contrary to expectations, physiological and tumor angiogenesis was not significantly affected by the absence of either EIIIA or EIIIB splice variants. Tumor growth was also not affected. In addition, the expression levels of smooth muscle alpha actin, believed to be modulated by EIIIA-containing fibronectins, were not affected either. Our experiments show that despite their tight regulation during angiogenesis, the presence of EIIIA or EIIIB splice variants individually is not essential for neovascularization.
Astrof
Sophie
S
Howard Hughes Medical Institute, Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Crowley
Denise
D
George
Elizabeth L
EL
Fukuda
Tomohiko
T
Sekiguchi
Kiyotoshi
K
Hanahan
Douglas
D
Hynes
Richard O
RO
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D005091:Exons / Q000235:genetics*; D005353:Fibronectins / Q000235:genetics* / Q000378:metabolism*; D007515:Islets of Langerhans / Q000098:blood supply; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000098:blood supply; D012171:Retinal Vessels / Q000254:growth & development; D013623:Tail / Q000098:blood supply
D005353:Fibronectins