CD99 acts as an oncosuppressor in osteosarcoma.
CD99 was recently reported to be under control of the osteoblast-specific transcription factor Cbfa1 (RUNX2) in osteoblasts, suggesting a role in the phato-physiology of these cells. No extensive information is available on the role(s) of this molecule in malignant phenotype, and osteosarcoma, in particular, has never been studied. We report that in 11 different cell lines and 17 clinical samples CD99 expression is either undetectable or very low. Being expressed in the normal counterpart, we tested the hypothesis that CD99 down-regulation may have a role in osteosarcoma development and progression. CD99-forced expression in two osteosarcoma cell lines significantly reduced resistance to anoikis, inhibited growth in anchorage independence as well as cell migration, and led to abrogation of tumorigenic and metastatic ability. Therefore, the molecule acts as a potent suppressor of malignancy in osteosarcoma. CD99 gene transfection induces caveolin-1 up-regulation and the two molecules were found to colocalize on the cell surface. Treatment with antisense oligonucleotides to caveolin-1 abrogates the effects of CD99 on migration. The findings point to an antioncogenic role for CD99 in osteosarcoma, likely through the regulation of caveolin-1 and inhibition of c-Src kinase activity.
Manara
Maria Cristina
MC
Laboratorio di Ricerca Oncologica, Istituti Ortopedici Rizzoli, Bologna, 40136 Italy.
Bernard
Ghislaine
G
Lollini
Pier-Luigi
PL
Nanni
Patrizia
P
Zuntini
Monia
M
Landuzzi
Lorena
L
Benini
Stefania
S
Lattanzi
Giovanna
G
Sciandra
Marika
M
Serra
Massimo
M
Colombo
Mario Paolo
MP
Bernard
Alain
A
Picci
Piero
P
Scotlandi
Katia
K
D000071443:12E7 Antigen; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D001859:Bone Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051242:Caveolin 1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D010006:Osteoblasts / Q000378:metabolism; D012516:Osteosarcoma / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D000071443:12E7 Antigen; D015703:Antigens, CD; C061828:CD99 protein, human; D051242:Caveolin 1; D015815:Cell Adhesion Molecules; D025521:Tumor Suppressor Proteins