Inhibition of tumor growth in mice by endostatin derived from abdominal transplanted encapsulated cells.
Endostatin, a C-terminal fragment of collagen 18a, inhibits the growth of established tumors and metastases in vivo by inhibiting angiogenesis. However, the purification procedures required for large-scale production and the attendant cost of these processes, together with the low effectiveness in clinical tests, suggest that alternative delivery methods might be required for efficient therapeutic use of endostatin. In the present study, we transfected Chinese hamster ovary (CHO) cells with a human endostatin gene expression vector and encapsulated the CHO cells in alginate-poly-L-lysine microcapsules. The release of biologically active endostatin was confirmed using the chicken chorioallantoic membrane assay. The encapsulated endostatin-expressing CHO cells can inhibit the growth of primary tumors in a subcutaneous B16 tumor model when injected into the abdominal cavity of mouse. These results widen the clinical application of the microencapsulated cell endostatin delivery system in cancer treatment.
Teng
Huaining
H
Institute of Biochemistry and Cell Biology, Model Organism Research Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Zhang
Ying
Y
Wang
Wei
W
Ma
Xiaojun
X
Fei
Jian
J
D000464:Alginates; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001672:Biocompatible Materials; D016466:CHO Cells / Q000378:metabolism* / Q000637:transplantation; D002214:Capsules / Q000627:therapeutic use; D043170:Collagen Type XVIII / Q000235:genetics / Q000627:therapeutic use*; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D043169:Endostatins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008546:Melanoma, Experimental / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010446:Peptide Fragments / Q000235:genetics / Q000627:therapeutic use*; D010529:Peritoneal Cavity; D011107:Polylysine / Q000031:analogs & derivatives; D014162:Transfection; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000464:Alginates; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D002214:Capsules; D043170:Collagen Type XVIII; D043169:Endostatins; D010446:Peptide Fragments; C051546:alginate-polylysine-alginate; D011107:Polylysine