Antiangiogenic and antitumor effects of endostatin on follicular thyroid carcinoma.
Tumor growth and metastasis depend on blood supply and blood vessel formation. Angiogenesis, therefore, represents a promising target for cancer therapy. Endostatin is one of the most potent antiangiogenic factors and has been shown to effectively inhibit angiogenesis and tumor growth in a variety of in vivo models. In this study, we tested the effects of endostatin on xenografted human follicular thyroid carcinoma (FTC) in nude mice. Our result demonstrated that recombinant endostatin significantly inhibited the growth of FTC xenografts. Furthermore, we established an endostatin-expressing FTC cell line (FTC-BmEndo) using retrovirus-mediated gene transfer approach. We found that the in vivo growth of FTC-BmEndo cells was significantly inhibited, compared with the parental FTC cells, whereas both lines grew at the same rate in vitro. High-level expression of endostatin within the FTC-BmEndo tumors was evidenced by immunohistochemical staining, paralleled with a reduced microvessel density. The systemic level of vascular endothelial growth factor was significantly lower in mice bearing the FTC-BmEndo tumors than in those bearing parental FTC tumors. By using two different approaches, namely the recombinant endostatin protein and the gene therapy strategy, our study demonstrated that endostatin could be effective in suppressing the growth of human FTC in immunodeficient mice.
Ye
Caisheng
C
Department of Vascular Surgery, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, Guangdong 510075, China.
Feng
Chong
C
Wang
Shenming
S
Liu
Xiaoning
X
Lin
Yongjie
Y
Li
Mengfeng
M
D018263:Adenocarcinoma, Follicular / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003094:Collagen / Q000097:blood / Q000235:genetics / Q000627:therapeutic use*; D043169:Endostatins; D016228:Endothelial Growth Factors / Q000097:blood; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000097:blood; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000097:blood / Q000235:genetics / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D043169:Endostatins; D016228:Endothelial Growth Factors; D008222:Lymphokines; D010446:Peptide Fragments; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D003094:Collagen