Faculty Profiles - TAKIGAWA Masaharu

Papers - TAKIGAWA Masaharu

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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 Reviewed

M TAKIGAWA, H PAN, A KINOSHITA, K TAJIMA, Y TAKANO

INTERNATIONAL JOURNAL OF CANCER 48 ( 5 ) 717 - 725 1991.7

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-LISS

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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Establishment from a human chondrosarcoma of a new immortal cell line with abilities to form proteoglycan-rich cartilage nodules and to respond to insulin in vitro and high tumorigenicity in vivo. Reviewed

Takigawa, M, Pan, H-O, Kinoshita, A, Tajima, K, Takano, Y

Int. J. Cancer 48 717 - 725 1991

INDUCTION OF ANGIOGENESIS IN CHICK YOLK-SAC MEMBRANE BY POLYAMINES AND ITS INHIBITION BY TISSUE INHIBITORS OF METALLOPROTEINASES (TIMP AND TIMP-2) Reviewed

M TAKIGAWA, Y NISHIDA, F SUZUKI, J KISHI, K YAMASHITA, T HAYAKAWA

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 171 ( 3 ) 1264 - 1271 1990.9

EFFECTS OF TUMOR NECROSIS FACTOR-ALPHA ON PROLIFERATION AND EXPRESSION OF DIFFERENTIATED PHENOTYPES IN RABBIT COSTAL CHONDROCYTES IN CULTURE Reviewed

M ENOMOTO, HO PAN, A KINOSHITA, Y YUTANI, F SUZUKI, M TAKIGAWA

CALCIFIED TISSUE INTERNATIONAL 47 ( 3 ) 145 - 151 1990.9

TUMOR ANGIOGENESIS AND POLYAMINES - ALPHA-DIFLUOROMETHYLORNITHINE, AN IRREVERSIBLE INHIBITOR OF ORNITHINE DECARBOXYLASE, INHIBITS B16 MELANOMA-INDUCED ANGIOGENESIS INOVO AND THE PROLIFERATION OF VASCULAR ENDOTHELIAL-CELLS INVITRO Reviewed

M TAKIGAWA, M ENOMOTO, Y NISHIDA, HO PAN, A KINOSHITA, F SUZUKI

CANCER RESEARCH 50 ( 13 ) 4131 - 4138 1990.7

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 Reviewed

M ENOMOTO, H PAN, F SUZUKI, M TAKIGAWA

JOURNAL OF BIOCHEMISTRY 107 ( 5 ) 743 - 748 1990.5

A CLONAL HUMAN CHONDROSARCOMA CELL-LINE PRODUCES AN ANTI-ANGIOGENIC ANTITUMOR FACTOR Reviewed

M TAKIGAWA, HO PAN, M ENOMOTO, A KINOSHITA, Y NISHIDA, F SUZUKI, K TAJIMA

ANTICANCER RESEARCH 10 ( 2A ) 311 - 315 1990.3

Insulin-like growth factors (]G0001[) and (]G0002[) are autocrine factors in stimulating proteoglycan synthesis, a marker of differentiated chondrocytes, acting through their respective receptors on a clonal human. chondrosarcoma-derived chondrocyte ce・・・ Reviewed

Takigawa, M, Kinoshita, A, Enomoto, M, Asada, A, Suzuki, F

Endocrinology 138 4390 - 4400 1990

POLYAMINES AND ANGIOGENESIS - INHIBITION OF TUMOR ANGIOGENESIS BY THE IRREVERSIBLE INHIBITOR OF ORNITHINE DECARBOXYLASE, ALPHA-DIFLUOROMETHYLORNITHINE Reviewed

M TAKIGAWA, M ENOMOTO, Y NISHIDA, HO PAN, A KINOSHITA, F SUZUKI

BIOLOGY AND CHEMISTRY OF POLYAMINES 12 203 - 211 1990

ESTABLISHMENT FROM MOUSE GROWTH CARTILAGE OF CLONAL CELL-LINES WITH RESPONSIVENESS TO PARATHYROID-HORMONE, ALKALINE-PHOSPHATASE ACTIVITY, AND ABILITY TO PRODUCE AN ENDOTHELIAL-CELL GROWTH INHIBITOR Reviewed

M TAKIGAWA, E SHIRAI, M ENOMOTO, A KINOSHITA, HO PAN, F SUZUKI, Y YUGARI

CALCIFIED TISSUE INTERNATIONAL 45 ( 5 ) 305 - 313 1989.11

DEMONSTRATION OF RECEPTORS FOR PARATHYROID-HORMONE ON CULTURED RABBIT COSTAL CHONDROCYTES Reviewed

M ENOMOTO, A KINOSHITA, HO PAN, F SUZUKI, YAMAMOTO, I, M TAKIGAWA

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 162 ( 3 ) 1222 - 1229 1989.8

ESTABLISHMENT OF A CLONAL HUMAN CHONDROSARCOMA CELL-LINE WITH CARTILAGE PHENOTYPES Reviewed

M TAKIGAWA, K TAJIMA, HO PAN, M ENOMOTO, A KINOSHITA, F SUZUKI, Y TAKANO, Y MORI

CANCER RESEARCH 49 ( 14 ) 3996 - 4002 1989.7

The distribution of differentiated phenotypes of chondrocytes in osteoarthritic hip. Reviewed

Yutani, Y, Asada, K, Takigawa, M, Omori, K, Shimazu, A, The distribution of, differentiated phenotypes of chondrocytes in osteoarthritic hip

Jpn.J.Rheum.Joint Surg. 8 179 - 186 1989

PARATHYROID HORMONE-RESPONSIVE CLONAL CELL-LINES FROM MOUSE GROWTH CARTILAGE Reviewed

M TAKIGAWA, E SHIRAI, M ENOMOTO, A KINOSHITA, F SUZUKI

NEW ACTIONS OF PARATHYROID HORMONE 423 - 428 1989

Cartilage-derived anti-tumor factor (CATF) - Partial purification and correlation of inhibitory activity against tumor growth with anti-angiogenic activity Reviewed

Masaharu Takigawa, Eiji Shirai, Motomi Enomoto, Yuji Hiraki, Fujio Suzuki, Tsuyoshi Shiio, Yasumi Yugari

Journal of Bone and Mineral Metabolism 6 ( 2 ) 29 - 38 1988.8

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer-Verlag

Cartilage-derived anti-tumor factor (CATF) inhibits the proliferation and DNA synthesis of bovine pulmonary artery endothelial (BPAE) cells in culture (Takigawa, M. et al. Cell. Biol. Inn. Rep., 9, 619-625, 1985). In the present study, we partially purified CATF by monitoring inhibition of DNA synthesis in BPAE cells and tested the effects of the purified materials on the growth of solid tumors and tumor-induced angiogenesis. Crude CATF (CATF20-300k), the fraction of 20 k to 300 k daltons, separated by ultrafiltration was further separated into three fractions by ultrafiltration. The fraction of 100 k to 300 k daltons (CATF100-300k) caused slightly more inhibition than CATF20-300k of DNA synthesis in BPAE cells. On the other hand, the fraction of 20 k to 50 k daltons had only a slight effect, and the fraction of 50 k to 100 k had even less effect on DNA synthesis in BPAE cells. CATF100-300k caused slightly more inhibition than CATF20-300k of the growth of solid tumors of B16 melanoma, while the fraction of 20 k to 100 k daltons did not inhibit the growth of tumors at all. CATF100-300k also inhibited B16 melanoma-induced angiogenesis in chick embryo chorioallantoic membranes (CAM), whereas the fraction of 20 k to 100 k daltons had little effect on the angiogenesis. CATF100-300k was further purified by DEAE-Sepharose CL-6B chromatography. The main peak with activity on DNA synthesis in BPAE cells was eluted with 0.3 to 0.35 M NaCl at pH 8.0. The activity of this peak on DNA synthesis in BPAE cells was about 70 fold that of CATF100-300k. The purified CATF also inhibited the growth of B16 melanoma and B16 melanoma-induced angiogenesis in CAM. On the other hand, the inactive fraction on DNA synthesis in BPAE cells obtained by DEAE-Sepharose chromatography was also inactive in inhibiting the growth of B16 melanoma and B16 melanoma-induced angiogenesis in CAM. These findings strongly suggest that CATF is an anionic macromolecule(s) and has anti-angiogenic activity, thereby inhibiting the growth of solid tumors. © 1988 Japanese Society of Bone Metabolism Research.

DOI： 10.1007/BF02375643

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DIFFERENTIAL-EFFECTS OF 1-ALPHA,25-DIHYDROXYCHOLECALCIFEROL AND 24R,25-DIHYDROXYCHOLECALCIFEROL ON THE PROLIFERATION AND THE DIFFERENTIATED PHENOTYPE OF RABBIT COSTAL CHONDROCYTES IN CULTURE Reviewed

M TAKIGAWA, M ENOMOTO, E SHIRAI, Y NISHII, F SUZUKI

ENDOCRINOLOGY 122 ( 3 ) 831 - 839 1988.3

HYDROCORTISONE STIMULATION OF PROLIFERATION AND GLYCOSAMINOGLYCAN SYNTHESIS IN RABBIT CRANIOFACIAL CHONDROCYTES INVITRO Reviewed

M TAKIGAWA, T TAKANO, K NAKAGAWA, M SAKUDA, F SUZUKI

ARCHIVES OF ORAL BIOLOGY 33 ( 12 ) 893 - 899 1988

Enhanced responsiveness to parathyroid hormone and induction of functional differentiation of cultured rabbit costal chondrocytes by a pulsed electromagnetic field

Yuji Hiraki, Naoto Endo, Masaharu Takigawa, Akira Asada, Hideaki Takahashi, Fujio Suzuki

BBA - Molecular Cell Research 931 ( 1 ) 94 - 100 1987.10

Language：English Publishing type：Research paper (scientific journal)

Pulsed electromagnetic fields promote healing of delayed united and ununited fractures by triggering a series of events in fibrocartilage. We examined the effects of a pulsed electromagnetic field (recurrent bursts, 15.4 Hz, of shorter pulses of an average of 2 gauss) on rabbit costal chondrocytes in culture. A pulsed electromagnetic field slightly reduced the intracellular cyclic adenosine 3′,5′-monophosphate (cAMP) level in the culture. However, it significantly enhanced cAMP accumulation in response to parathyroid hormone (PTH) to 140% of that induced by PTH in its absence, while it did not affect cAMP accumulation in response to prostaglandin E1 or prostaglandin I2. The effect on cAMP accumulation in response to PTH became evident after exposure of the cultures to the pulsed electromagnetic field for 48 h, and was dependent upon the field strength. cAMP accumulation in response to PTH is followed by induction of ornithine decarboxylase, a good marker of differentiated chondrocytes, after PTH treatment for 4 h. Consistent with the enhanced cAMP accumulation, ornithine decarboxylase activity induced by PTH was also increased by the pulsed electromagnetic field to 170% of that in cells not exposed to a pulsed electromagnetic field. Furthermore, stimulation of glycosaminoglycan synthesis, a differentiated phenotype, in response to PTH was significantly enhanced by a pulsed electromagnetic field. Thus, a pulsed electromagnetic field enhanced a series of events in rabbit costal chondrocytes in response to PTH. These findings show that exposure of chondrocytes to a pulsed electromagnetic field resulted in functional differentiation of the cells. © 1987.

DOI： 10.1016/0167-4889(87)90054-1

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ENHANCED RESPONSIVENESS TO PARATHYROID-HORMONE AND INDUCTION OF FUNCTIONAL-DIFFERENTIATION OF CULTURED RABBIT COSTAL CHONDROCYTES BY A PULSED ELECTROMAGNETIC-FIELD Reviewed

Y HIRAKI, N ENDO, M TAKIGAWA, A ASADA, H TAKAHASHI, F SUZUKI

BIOCHIMICA ET BIOPHYSICA ACTA 931 ( 1 ) 94 - 100 1987.10

CHONDROCYTES DEDIFFERENTIATED BY SERIAL MONOLAYER-CULTURE FORM CARTILAGE NODULES IN NUDE-MICE Reviewed

M TAKIGAWA, E SHIRAI, K FUKUO, K TAJIMA, Y MORI, F SUZUKI

BONE AND MINERAL 2 ( 6 ) 449 - 462 1987.9

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