Specific loss of chondromodulin-I gene expression in chondrosarcoma and the suppression of tumor angiogenesis and growth by its recombinant protein in vivo.
Chondromodulin-I (ChM-I) was previously identified as an angiogenesis inhibitor in cartilage. Here, we demonstrated that the level of ChM-I transcripts was substantially reduced to 100 or even less in the lower-grade chondrosarcomas, in articular cartilage or other benign cartilage tumors. We implanted human chondrosarcoma OUMS-27 cells into nude mice that reproducibly produced tumors with cartilaginous matrix. Tumor-induced angiogenesis was evident when the tumors were excised 30 days after implantation. However, the local administration of recombinant human ChM-I almost completely blocked vascular invasion and tumor growth in vivo. Moreover, ChM-I also inhibited the growth of HT-29 colon adenocarcinoma in vivo, implying its therapeutic potential for solid tumors.
Hayami
T
T
Department of Orthopaedic Surgery, Niigata University School of Medicine, Japan.
Shukunami
C
C
Mitsui
K
K
Endo
N
N
Tokunaga
K
K
Kondo
J
J
Takahashi
H E
HE
Hiraki
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001859:Bone Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000473:pathology; D002356:Cartilage / Q000473:pathology; D002813:Chondrosarcoma / Q000098:blood supply / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006133:Growth Substances / Q000032:analysis / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C489408:Cnmd protein, mouse; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C068675:CNMD protein, human