Anti-chondrosarcoma effects of PEDF mediated via molecules important to apoptosis, cell cycling, adhesion and invasion.
Chondrosarcoma develops as a result of overgrowth of chondrocytes and overproduction of cartilage matrix. It is currently surgically treated, although non-invasive methods are being sought. In this report, pigment epithelium-derived factor (PEDF) induced apoptosis in the chondrosarcoma cell line - JJ012, with upregulation of Bax, Fas, caspase-3 and -6 and downregulation of Bcl-2. Cell cycling was also decreased with decreased expression of p38, p-Akt, p-Erk and JNK1 and increased expression of p73 and E2F1. Furthermore, PEDF increased adhesion of cells to collagen-I, with decreased expression of p-Fak, RhoA and cdc42. Invasion of cells through collagen-I was also reduced by PEDF, with decreased expression of uPAR, MMP-14 and increased expression of PAI-1. These findings seminally indicate that PEDF may have potential as an anti-cancer agent against chondrosarcoma.
Tan
Mei Lin
ML
Department of Orthopaedics, St. Vincent's Hospital Melbourne, VIC, Australia.
Choong
Peter F M
PF
Dass
Crispin R
CR
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002813:Chondrosarcoma / Q000188:drug therapy* / Q000473:pathology; D005136:Eye Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000627:therapeutic use*; D015843:Serpins / Q000494:pharmacology / Q000627:therapeutic use*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
D000970:Antineoplastic Agents; D005136:Eye Proteins; D051417:Focal Adhesion Kinase 1; D009414:Nerve Growth Factors; D015843:Serpins; D020764:cdc42 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein; D000099174:Pigment Epithelium-Derived Factor; C066737:RHOA protein, human; C496050:PTK2 protein, human