Molecular profiling of human chondrosarcomas for matrix production and cancer markers.
Chondrosarcoma is the second most common malignant bone tumor, characterized by production of abundant extracellular matrix resembling hyaline cartilage. To better understand the molecular pathogenesis of chondrosarcoma, we analyzed 12 chondrosarcomas for their production of connective tissue components and SOX9, a key regulator of normal chondrocyte differentiation. Furthermore, 10 chondrosarcoma samples were screened for additional changes in gene expression using cDNA array analysis. In Northern analysis, several tumors were found to express type II collagen mRNA at levels comparable to fetal cartilage used as a control. Interestingly, the highest levels of type II collagen mRNA were seen in 2 of the 3 grade 3 chondrosarcomas, which also exhibited the highest mRNA levels of SOX9 and "prechondrogenic" pro alpha 1(IIA) collagen. Expression of SOX9 in human chondrosarcomas is novel and suggests that chondrosarcomas originate from a multipotent stem cell committed to differentiation along the chondrogenic pathway. Results of the cDNA array analyses emphasize the heterogeneous nature of chondrosarcoma as no single transcript was systematically up- or downregulated in all tumors analyzed. Among the interesting changes observed was upregulation of decorin mRNA in 7 of the 10 tumors analyzed. Further studies are needed to determine whether decorin plays a role in the pathogenesis of chondrosarcoma. The cDNA arrays also revealed discrepancies from Northern and RNase protection analyses in transcript levels of matrix components, emphasizing the need to validate cDNA array data with other techniques.
Skeletal Research Program, Department of Medical Biochemistry and Molecular Biology, University of Turku, Turku, Finland.
Mirva
M
Söderström
Tom
T
Böhling
Tauno
T
Ekfors
Lassi
L
Nelimarkka
Hannu T
HT
Aro
Eero
E
Vuorio
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D015152:Blotting, Northern; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D002813:Chondrosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006609:High Mobility Group Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000302:isolation & purification; D055758:SOX9 Transcription Factor; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000502:physiology
D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; D006609:High Mobility Group Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D014157:Transcription Factors