ESTABLISHMENT FROM A HUMAN CHONDROSARCOMA OF A NEW IMMORTAL CELL-LINE WITH HIGH TUMORIGENICITY INVIVO, WHICH IS ABLE TO FORM PROTEOGLYCAN-RICH CARTILAGE-LIKE NODULES AND TO RESPOND TO INSULIN INVITRO

被引:65
作者
TAKIGAWA, M
PAN, H
KINOSHITA, A
TAJIMA, K
TAKANO, Y
机构
[1] SAISEIKAI NAKATSU HOSP,OSAKA 530,JAPAN
[2] HOKKAIDO UNIV,DEPT ORAL ANAT 2,SAPPORO,HOKKAIDO 060,JAPAN
关键词
D O I
10.1002/ijc.2910480515
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The human chondrosarcoma cell line (HCS-2/8) established by our group expresses cartilage phenotypes such as production of cartilage-type proteoglycans and collagen type II, but its tumorigenicity is low. To develop an in vitro experimental system for studies of human chondrosarcomas, a new immortal cell line of human chondrosarcoma, named HCS-2/A, was established from the same tumor. HCS-2/A cells proliferated with a doubling time of 3 1/2 days in a medium containing 20% fetal bovine serum (FBS). This growth rate was comparable to that of HCS-2/8 cells. However, HCS-2/A cells proliferated more rapidly than HCS-2/8 cells in the presence of 2-10% FBS. Like HCS-2/8 cells, HCS-2/A cells had a polygonal shape in sparse cultures and became spherical as they reached confluence, after which they formed nodules composed of multilayered cells and a large quantity of extracellular matrix showing strong metachromasia. The nodules formed by HCS-2/A cells were thicker and also larger in diameter than those formed by HCS-2/8 cells. Electron microscopically, the cells in the nodules resembled chondrocytes in vivo, but each cell had an irregular-shaped nucleus which is a characteristic of tumor cells. The cells actively synthesized "cartilage-specific" large proteoglycans and their level of proteoglycan synthesis was comparable to that of HCS-2/8 cells. Insulin, which stimulates proteoglycan and DNA syntheses in cultured chondrocytes, markedly increased proteoglycan synthesis in HCS-2/A cells. On the other hand, the hormone only slightly increased proteoglycan synthesis in HCS-2/8 cells. Insulin also stimulated DNA synthesis in cultured HCS-2/A cells, but not in HCS-2/8 cells. Immunostaining revealed that HCS-2/A cells produced type-II collagen but not type-I collagen. However, the level of collagen synthesis of HCS-2/A cells was lower than that of HCS-2/8 cells. Inoculation of HCS-2/A cells into athymic mice resulted in the formation of chondrosarcomas that grew faster than those arising from HCS-2/8 cells.
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页码:717 / 725
页数:9
相关论文
共 35 条
[1]  
BARRETT JC, 1990, J CELL BIOCHEM S, V14, P253
[2]   DEDIFFERENTIATED CHONDROCYTES REEXPRESS THE DIFFERENTIATED COLLAGEN PHENOTYPE WHEN CULTURED IN AGAROSE GELS [J].
BENYA, PD ;
SHAFFER, JD .
CELL, 1982, 30 (01) :215-224
[3]   COLLAGEN HETEROGENEITY IN HUMAN CARTILAGE - IDENTIFICATION OF SEVERAL NEW COLLAGEN CHAINS [J].
BURGESON, RE ;
HOLLISTER, DW .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1979, 87 (04) :1124-1131
[4]   EFFECTS OF TUMOR NECROSIS FACTOR-ALPHA ON PROLIFERATION AND EXPRESSION OF DIFFERENTIATED PHENOTYPES IN RABBIT COSTAL CHONDROCYTES IN CULTURE [J].
ENOMOTO, M ;
PAN, HO ;
KINOSHITA, A ;
YUTANI, Y ;
SUZUKI, F ;
TAKIGAWA, M .
CALCIFIED TISSUE INTERNATIONAL, 1990, 47 (03) :145-151
[5]   PHYSIOLOGICAL-ROLE OF VITAMIN-A IN GROWTH CARTILAGE CELLS - LOW CONCENTRATIONS OF RETINOIC ACID STRONGLY PROMOTE THE PROLIFERATION OF RABBIT COSTAL GROWTH CARTILAGE CELLS IN CULTURE [J].
ENOMOTO, M ;
PAN, H ;
SUZUKI, F ;
TAKIGAWA, M .
JOURNAL OF BIOCHEMISTRY, 1990, 107 (05) :743-748
[6]  
HIRAKI Y, 1985, BIOCHEM INT, V10, P267
[7]   DIFFERENTIAL-EFFECTS OF PARATHYROID-HORMONE AND SOMATOMEDIN-LIKE GROWTH-FACTORS ON THE SIZES OF PROTEOGLYCAN MONOMERS AND THEIR SYNTHESIS IN RABBIT COSTAL CHONDROCYTES IN CULTURE [J].
HIRAKI, Y ;
YUTANI, Y ;
TAKIGAWA, M ;
KATO, Y ;
SUZUKI, F .
BIOCHIMICA ET BIOPHYSICA ACTA, 1985, 845 (03) :445-453
[8]   SERUM-FREE MEDIUM SUPPLEMENTED WITH MULTIPLICATION-STIMULATING ACTIVITY (MSA) SUPPORTS BOTH PROLIFERATION AND DIFFERENTIATION OF CHONDROCYTES IN PRIMARY CULTURE [J].
KATO, Y ;
NASU, N ;
TAKASE, T ;
DAIKUHARA, Y ;
SUZUKI, F .
EXPERIMENTAL CELL RESEARCH, 1980, 125 (01) :167-174
[9]  
LEVOVITZ HE, 1975, VITAM HORM, V33, P575
[10]  
LOWRY OH, 1951, J BIOL CHEM, V193, P265