Endostatin expression by MDA-MB-435 breast cancer cells effectively inhibits tumor growth.
Tumors must induce the formation of new blood vessels in order to grow and metastasize. Endostatin, a cleaved product of collagen XVIII, inhibits endothelial cell proliferation and suppresses tumor growth and metastases. Several recent reports have questioned the efficacy of endostatin as a tumor suppressor in experimental animals. Our objective was to determine whether endostatin expression in breast cancer cells inhibits neovascularization and tumor growth in nude mice. MDA-MB-435 cells were transfected with an endostatin expression vector while control cells were transfected with an empty vector. Endostatin expression and secretion were confirmed by RT-PCR and a dot blot assay. No differences were observed in the growth rates of the endostatin-expressing and control clones in vitro. When injected into male and female nude mice, tumors from the control clones increased in size 10-15 fold over 8-10 weeks. In contrast, the endostatin clones formed small tumors which did not increase in size after the first 3 weeks. The endostatinderived tumors had a significantly higher apoptotic index (5.6%) compared to controls (2.0%) and showed a marked reduction in vascularization. In conclusion, expression of endostatin in MDA-MB-435 breast cancer cells effectively suppressed breast tumor growth by inhibiting angiogenesis and increasing apoptosis.
Liby
Karen
K
Department of Cell Biology, University of Cincinnati Medical School, Ohio 45267-0521, USA.
Neltner
Bonnie
B
Mohamet
Lisa
L
Burd
Craig
C
Ben-Jonathan
Nira
N
D020533:Angiogenesis Inhibitors / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D003094:Collagen / Q000235:genetics* / Q000378:metabolism; D043170:Collagen Type XVIII; D017931:DNA Primers / Q000737:chemistry; D043169:Endostatins; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000517:prevention & control*; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured; D014841:von Willebrand Factor / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D043170:Collagen Type XVIII; D017931:DNA Primers; D043169:Endostatins; D010446:Peptide Fragments; D014841:von Willebrand Factor; D003094:Collagen