title: The disintegrin echistatin in combination with doxorubicin targets high-metastatic human osteosarcoma overexpressing ανβ3 integrin in chick embryo and nude mouse models.
abstract: Echistatin, a cyclic RGD peptide, which is an antagonist of αvβ3 integrin (disintegrin), inhibited human osteosarcoma in the chick chorioallontoic membrane (CAM) model and tumor growth and pulmonary metastases in a nude mouse orthotopic model. A high-metastatic variant of human osteosarcoma, 143B-LM4, overexpressing αvβ3 integrin was used. Tumor angiogenesis by high-metastatic variant 143B-LM4 cells in the CAM was significantly inhibited by echistatin (P<0.05) as was overall growth. A doxorubicin (DOX)-echistatin combination inhibited orthotopic tumor growth compared to untreated control (P<0.01) or DOX alone (P<0.05) in nude mice. Tumor-bearing mice treated with the DOX-echistatin combination survived longer than those treated with DOX alone or control PBS (P<0.01 and P<0.01, respectively). Echistatin also inhibited experimental lung metastasis of 143B-LM4 cells in nude mice. These results suggest that DOX in combination with a disintegrin has potential to treat osteosarcoma and that αvβ3 integrin may be a target for osteosarcoma.
authors.affiliation: AntiCancer, Inc., San Diego, CA 92111, USA.|Department of Surgery, University of California, San Diego, CA 92103, USA.|Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, 903-0125 Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Tome
authors.affiliation: AntiCancer, Inc., San Diego, CA 92111, USA.|Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, 920-8641 Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Department of Physiology, Graduate School of Medical Science, Kanazawa University, Kanazawa, 920-8641 Japan.
authors.forename: Naotoshi
authors.initials: N
authors.lastname: Sugimoto
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, 920-8641 Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuchiya
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, 903-0125 Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Kanaya
authors.affiliation: Department of Surgery, University of California, San Diego, CA 92103, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
authors.affiliation: AntiCancer, Inc., San Diego, CA 92111, USA.|Department of Surgery, University of California, San Diego, CA 92103, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002642:Chick Embryo; D004317:Doxorubicin / Q000008:administration & dosage*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D036341:Intercellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D010455:Peptides / Q000008:administration & dosage*
chemical_list: D039302:Integrin alphaVbeta3; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C057986:echistatin; D004317:Doxorubicin
keywords: echistatin; green fluorescent protein; nude mice; orthotopic; osteosarcoma; red fluorescent protein; αvβ3 integrin