血管平滑筋形質転換におけるβ2-カイメリンを介した細胞内情報伝達の解析

• 研究課題/領域番号: 13832007
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 細胞生物学
• 研究機関: 久留米大学
• 研究代表者: 加藤 誠也 久留米大学, 医学部, 助教授 (60268844)
• 研究分担者: 藤井 輝彦 久留米大学, 医学部, 講師 (50199288)
• 研究期間 (年度): 2001 – 2003
• 研究課題ステータス: 完了 (2003年度)
• 配分額: 3,600千円 (直接経費: 3,600千円); 2003年度: 1,300千円 (直接経費: 1,300千円); 2002年度: 1,000千円 (直接経費: 1,000千円); 2001年度: 1,300千円 (直接経費: 1,300千円)
• キーワード: 血管平滑筋細胞 / β2-カイメリン / プロテインキナーゼC / 形質転換 / 動脈硬化 / プロテインキナーゼ C

研究概要

動脈硬化形成時に血管平滑筋細胞形質転換はkey eventで、病変部の活性化増殖因子は、特異的レセプターを介し形質転換を制御する。チロシンキナーゼ型レセプターはphospholipase Cリン酸化とイノシトール代謝回転亢進を経てdiacylglycerol(DG)を産生するが、従来より内因性DGの唯一の標的は、発癌物質phorbol esterの細胞質内レセプターprotein kinase C(PKC)と考えられていた。近年、低分子量G蛋白であるRacに対するGTPase activating protein(GAP)として同定されたchimaerinが、PKC同様にDGやphorbol esterのTPAに高い親和性を示す事が報告され、平滑筋細胞におけるchimaerin発現と形質変化における意義を検討した。培養血管平滑筋細胞を用い、beta2-chimaerin発現をRT-PCR、Western blotting、免疫蛍光染色で、HA-tagged beta2-chimaerin発現adenovirus vector(Ad-Chim)を用いた過剰発現系で細胞増殖(細胞数計測、BrdU incorporation assay)と遊走能を検討した。培養ヒト平滑筋細胞は、対照ヒト神経膠腫細胞(U251MG)に比し少量ながら内因性beta2-chimaerin mRNA、蛋白を発現していた。Ad-Chim感染群(10-200M0l)は、TPA刺激によるchimaerin分子の凝集と細胞膜への移動を示し、PKC inhibitor(GF109203X)に影響されなかった。対照であるAd-LacZ感染群に比し、血清(10%FCS)、PDGF(10ng/ml)、bFGF(50ng/ml)刺激下の増殖、遊走が抑制された。beta2-cnimaerinシグナリングは血管平滑筋形質転換制御の一因と考えられる。

研究成果

• [文献書誌] Fujii T, Kato S, Yamana H, Tanaka Y, Fujita H, Shirouzu K, Morimatsu M.: "Expression of G1 cell cycle markers and the effect of adenovirus-mediated overexpression of p21Waf-1 in squamous cell carcinoma of the esophagus"Int J Oncol.. 18. 157-163 (2001)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Shibata R, Kai, H Seki Y, Kato S, Morimatsu M, Kaibuchi K, Imaizumi T.: "Role of Rho-associated protein kinase in neointima formation after vascular injury."Circulation. 103. 284-289 (2001)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Zemmyo N, Komiya S, Hamada T, Hiraoka K, Kato S, Fujii T, Yano H, Irie K, Nagata K.: "Transcriptional activation of p21 by vitamine D3 vitamine K2 lead to differentiation of p53-deficient MG-63 osteosarcoma cells."Hum Pathol. 32. 410-416 (2001)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Hamada T, Yoshida T, Kinjo I, Minoguchi S, Yasukawa H, Kato S, Mimata H, Nomura Y, Seki Y, Kubo M, Yoshimura A.: "A mutant form of JAB/SOCS1 auguments the cytokine-induced JAK/STAT pathway by accelerating degradation of wild-type JAB/CIS family protein through the SOCS-box."J Biol Chem. 276. 40746-40754 (2001)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Wada Y, Kato S, Okamoto K, Izumaru S, Aoyagi S, Morimatsu M.: "Diltiazem, a calcium antagonist, inhibits matrix metalloproteinase-1 (tissue collagenase) production and collagenolytic activity in human vascular smooth muscle cells."Int J Mol Med. 8. 561-566 (2001)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Kato S, Ueda S, Tamaki K, Fujii M, Miyazono K, ten Dijke P, Morimatsu M, Okuda S.: "Ectopic expression of Smad7 inhibits transforming growth factor-b responses in vascular smooth muscle cells."Life Sci. 69. 2641-2652 (2001)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Okamato M, Kato S, Oizumi K, Kinoshita M, Inoue Y, Hoshino K, Akira S, Mckenzie ANJ, Young HA, Hoshino T.: "IL-18 in synergy with IL-2 induces lethal lung injury in mice : A potential role for cytokines, chemokines and NK cells in the pathologenesis of interstitial pneumonia."Blood. 99. 1289-1299 (2001)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Hiraoka K, Zenmyo M, Komiya S, Kawabata R, Yokouchi M, Suzuki R, Hamada T, Kato S, Nagata K.: "Relationship of p21 (waf1/cip1) and differentiation in chondrosarcoma cells."Virchowa Arch. 440. 285-290 (2002)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Aoki T, Kato S, Fox FC, Okamoto K, Sakata K, Morimatsu M, Shigemori M.: "Inhibition of autocrine fibroblast growth factors signaling by the adenovirus-mediated expression of an antisense trangene or a dominant negative receptor in human glioma cells in vitro."Int J Oncol. 21. 629-636 (2002)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Sakata K, Kato S, Fox JC, Shigemori M, Morimatsu M.: "Autocrine singaling through Ras regulates cells survival activity in human glioma cells : Potential cross-talk between Ras and the phosphatidylinositol 3-kinase-Akt pathway."J Neuropath Exp Neurol. 61. 975-983 (2002)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Ueda S, Kato S, Matsuoka H, Kimoto M, Okuda S, Morimatsu M, Imaizumi T.: "Regulation of Cytokine-induced Nitric Oxide Synthesis by Asymmetric Dimethylarginine : Role of Dimethylarginine Dimethylaminohydrolase."Circ Res. 92. 226-233 (2003)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Ikedo H, Tamaki K, Ueda S, Kato S, Fujii M, ten Dijke P, Okuda S.: "Smad protein and TGF-β signaling in vascular smooth muscle cells."Int J Mol Med. 11. 645-650 (2003)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Shibata R, Kai H, Seki Y, Kato S, Wada Y, Hanakawa Y, Hasimoto K, Yoshimura A, Imaizumi T.: "Inhibition of STAT3 prevents neointima formation by inhibiting proliferation and promoting apoptosis of neointimal smooth muscle cells."Hum Gene Ther. 14. 601-610 (2003)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Kato S, Ueda S, Yamaguchi M, Miyamoto T, Fujii T, Izumaru S, Kume S, Toyozumi Y, Arima N, Morimatsu M.: "Overexpression of p21 Waf1 induces apoptosis in immortalized human vascular smooth muscle cells."J Atheroscler Thromb. 10. 239-245 (2003)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Kawase Y, Hoshino T, Yokota K, Kuzuhara A, Kiril Y, Nishiwaki E, Yu Maeda, Junji Takeda J, Okamoto M, Kato S, Imaizumi T, Aizawa H, Yoshino K.: "Exacerbated and Prolonged Allergic and Non-Allergic Inflammatory Cutaneous Reaction in Mice with Targeted IL-18 Expression in the Skin."J Invest Dermatol. 121. 502-509 (2003)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Koga A, Oka N, Kikuchi T, Miyazaki H, Kato S, Imaizumi T.: "Adenovirus-mediated overexpression of caveolin-3 inhibits rat cardiomyocyte hypertrophy."Hypertension. 42. 213-219 (2003)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Hoshino T, Nakamura H, Okamoto M, Kato S, Araya S, Nomiyama K, Oizumi K, Young HA. Aizawa H, Yodoi J.: "Redox-Active Protein Thioredoxin Prevents Proinflammatory Cytokin-or Bleomycin-Induced Lung Injury."Am J Resp Crit Care. 168. 1075-1083 (2003)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Hanada T, Yoshida H, Kato S, Tanaka K, Masutani K, Tsukada J, Nomura Y, Mimata H, Kubo M, Yoshimura A.: "Suppressor of cytokine signaling-1 (SOCS1) is essential for suppressing dendritic cell activation and systemic autoimmunity."Immunity. 19. 437-450 (2003)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Izumaru S, Arima N, Toyozumi Y, Kato S, Morimatsu M, Nakashima T.: "Down-regulation of p21 Waf-1 protein facilitates IR-and UV-induced apoptosis in human squamous carcinoma cells."Int J Oncol. 24. 1245-1255 (2004)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Okamoto K, Kato S, Arima N, Fuji T, Morimatsu M, Imaizumi T.: "Cyclin-dependent kinase inhibitor, p21 Waf1, regulates vascular smooth muscle cell hypertrophy."Hypertension Research. 27. 283-291 (2004)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Fujii T, Kato S, Yamana H, Tanaka Y, Fujita H, Shirouzu K, Morimatsu M.: "Expression of G1 cell cycle markers and the effect of adenovirusmediated overexpression of p2lWaf-1 in squamous cell carcinoma of the esophagus."Int J Oncol.. 18. 157-163 (2001)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Shibata R, Kai, H Seki Y, Kato S.Morimatsu M, Kaibuchi K, Imaizumi T.: "Role of Rho-associated protein kinase in neointima formation after vascular injury."Circulation. 103. 284-289 (2001)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Zemmyo N, Komiya S, Hamada T, Hiraoka K, Kato S, Fujii T, Yano H, Irie K, Nagata K.: "Transcriptional activation of p21 by vitamine D3 or vitamine K2 leads to differentiation of p53-deficient MG-63 osteosarcoma cells."Hum Pathol. 32. 410-416 (2001)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Hamada T, Yoshida T, Kinjo I, Minoguchi S, Yasukawa H, Kato S, Miinata H, Nomura Y, Seki Y, Kubo M, Yoshimura A.: "A mutant form of JAB/SOCS1 auguments the cytokine-induced JAK/STAT pathway by accelerating degradation of wild-type JAB/CIS family proteins through the SOCS-box."J Biol Chem. 276. 40746-40754 (2001)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Wada Y, Kato S.Okamoto K, Izumaru S.Aoyagi S, Morimatsu M.: "Diltiazem, a calcium antagonist, inhibits matrix metalloproteinase-1 (tissue collagenase) production and collagenolytic activity in human vascular smooth muscle cells."Int J Mol Med. 8. 561-566 (2001)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Kato S, Ueda S, Tamaki K, Fujii M, Miyazono K, ten Dijke P, Morimatsu M, Okuda S.: "Ectopic expression of Smad7 inhibits transforming growth factor-b responses in vascular smooth muscle cells."Life Sci. 69. 2641-2652 (2001)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Okamato M, Kato S, Oizumi K, Kinoshita M, Inoue Y, Hoshino K, Akira S, Mckenzie ANJ, Young HA, Hoshino T.: "IL-18 in synergy with IL-2 induces lethal lung injury in mice : A potential role for cytokines, chemokines and NK cells in the pathologenesis of interstitial pneumonia."Blood. 99. 1289-1298 (2002)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Hiraoka K, Zenmyo M, Komiya 5, Kawabata R, Yokouchi M, Suzuki R, Hamada T, Kato S, Nagata K.: "Relationship of p21(waf1/cip1) and differentiation in chondrosarcoma cells."Virchows Arch. 440. 285-290 (2002)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Aoki T, Kato S, Fox FC, Okamoto K, Sakata K, Morimatsu M, Shigemon M.: "Inhibition of autocrine fibroblast growth factor signaling by the adenovirus-mediated expression of an antisense trangene or a dominant negative receptor in human glioma cells in vitro."Int J Oncol. 21. 629-636 (2002)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Sakata K, Kato_S, Fox JC, Shigemori M, Morimatsu M.: "Autocrine signaling through Ras regulates cell survival activity in human glioma cells : Potential cross-talk between Ras and the phosphatidylinositol 3-kinase-Akt pathway."J Neuropath Exp Neurol. 61. 975-983 (2002)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Ueda 5, Kato S, Matsuoka H, Kimoto M, Okuda S, Morimatsu M, Imaizumi T.: "Regulation of Cytokine-induced Nitric Oxide Synthesis by Asymmetric Dimethylarginine : Role of Dimethylarginine Dimethylaminohydrolase."Circ Res. 92. 226-233 (2003)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Ikedo H, Tamaki K, Ueda S.Kato S, Fujii M, ten Dijke P, Okuda S.: "Smad protein and TOP-p signaling in vascular smooth muscle cells"Int J Mol Med. 11. 645-650 (2003)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Shibata R,, Kai H, Seki Y, Kato S, Wada Y, Hanakawa Y, Hashimoto K, Yoshimura A, Imaizumi T.: "Inhibition of STAT3 prevents neointima formation by inhibiting proliferation and promoting apoptosis of neointimal smooth muscle cells."Hum Gene Ther. 14. 601-610 (2003)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Kato S, Ueda S, Yamaguchi M, Miyamoto T, Fujii T, Izumaru S, Kume 5, Toyozumi Y, Anma N, Morimatsu M.: "Overexpression of p2lWaf1 induces apoptosis in immortalized human vascular smooth muscle cells."J Atheroscler Thromb. 10. 239-245 (2003)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Kawase Y, Hoshino T, Yokota K, Kuzuhara A, Kirii Y, Nishiwaki E, Yu Maeda, Junji Takeda J, Okamoto M, Kato S. Imaizumi T, Aizawa H, Yoshino K.: "Exacerbated and Prolonged Allergic and Non-Allergic Inflammatory Cutaneous Reaction in Mice with Targeted IL-18 Expression in the Skin."J Invest Dermatol. 121. 502-509 (2003)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Koga A, Oka N, Kikuchi T, Miyazaki H, Kato S, Imaizumi T.: "Adenovirus-mediated overexpression of caveolin-3 inhibits rat cardiomyocyte hypertrophy."Hypertension. 42. 213-219 (2003)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Hoshino T, Nakamura H, Okamoto M, Kato S.Araya S, Nomiyama K, Oizumi K, Young HA.Aizawa H, Yodoi J.: "Redox-Active Protein Thioredoxin Prevents Proinflammatory Cytokine-or Bleomycin-Induced Lung Injury."Am J Resp Crit Care. 168. 1075-1083 (2003)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Hanada T, Yoshida H, Kato S.Tanaka K, Masutani K, Tsukada J, Nomura Y, Mimata H, Kubo M, Yoshimura A.: "Suppressor of cytokine signaling-1 (SOCS1) is essential [or suppressing dendritic cell activation and systemic autoimmunity."Immunity. 19. 437-450 (2003)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Izumaru S, Arima N, Toyozumi Y, Kato S, Morimatsu M, Nakashima T.: "Down-regulation of p21Waf-1 protein facilitates IR-and UV-induced apoptosis in human squamous carcinoma cells."Int J Oncol. 24. 1245-1255 (2004)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Okamoto K, Kato S, Arima N, Fujii T, Morimatsu M, Imaizumi T.: "Cyclin-dependent kinase inhibitor, p21Waf1, regulates vascular smooth muscle cell hypertrophy."Hypertension Research. 27. 283-291 (2004)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Ikedo H, Tamaki K, Ueda S, Kato S, Fujii M, ten Dijke P, Okuda S: "Smad protein and TGF-β signaling in vascular smooth muscle cells"Int J Mol Med. 11. 645-650 (2003)
• [文献書誌] Kato S, Ueda S, Yamagnuhi M, Miyamoto T, Fujii T, Izumaru S, Kume S, Toyozumi Y, Arima N, Morimatsu M: "Overexpression of p21 Wafl induces apoptosis in immortalized human vascular smooth muscle cells"J Athevoscler Thromb. 10. 239-245 (2003)
• [文献書誌] Kawase Y, Hoshino T, Yokota K, Kuzuhara A, Kirli Y, Nishiwaki E, Yu Maeda, Junji Takeda J, Okamoto M, Kato S, Imaizumi T, Aizawa H, Yoshino K: "Exacerbated and Prolonged Allergic and Non-Allergic Inflammatory Cutaneous Reaction in Mice with Targeted IL-18 Expression in the Skin."J Invest Dermatol. 121. 502-509 (2003)
• [文献書誌] Koga A, Oka N, Kikuchi T, Miyazaki H, Kato S, Imaizumi T: "Adenovirus-mediated overexpression of caveolin-3 inhibits fat cardiomyocyte hypertrophy."Hypertension. 42. 213-219 (2003)
• [文献書誌] Hoshino T, Nakamura H, Okamoto M, Kato S, Araya S, Nomiyama K, Oizumi K, Young HA, Aizawa H, Yodoi J: "Redox-active Protein Thioredoxin Prevents Proinflammatory Cytokine-or Bleomycin-induced Lung Injury"Am J Resp Crit Care. 168. 1075-1083 (2003)
• [文献書誌] Hanada T, Yoshida H, Kato S, Tanaka K, Masutani K, Tsukada J, Nomura Y, Mimata H, Kubo M, Yoshimura A: "Suppressor of cytokine signaling-1 (SOCS1) is essential for suppressing dendritic cell activation and systemic autoimmunity"Immunity. 19. 437-450 (2003)
• [文献書誌] Okamoto M, Kato S, Oizumi K, Kinoshita M, Inoue Y, Hoshino K, Akira S, Mckenzie ANJ, Young HA, Hoshino T.: "IL-18 in synergy with IL-2 induces lethal lung injury in mice : A potential role for cytokines, chemokines and NK cells in the pathologenesis of interstitial pneumonia"Blood. 99. 1289-1298 (2002)
• [文献書誌] Fujii T, Sudo T, Sueyoshi S, Tanaka T, Fujita H, Shirouzu K, Ban S, Toyonaga A, Kato S, Yamana H.: "Clinicopathologic study of neovascularization and VEGF expression in superficial esophageal carcinoma"Int J Oncol. 21. 1181-1187 (2002)
• [文献書誌] Sakata K, Kato S, Fox JC, Shigemori M, Morimatsu M.: "Autocrine singaling through Ras regulates cell survival activity in human glioma cells : Potential cross-talk between Ras and the phosphatidylinositol 3-kinase-Akt pathway"J Neuropath Exp Neurol. 61. 975-983 (2002)
• [文献書誌] Aoki T, Kato S, Fox FC, Okamoto K, Sakata K, Morimatsu M, Shigemori M.: "Inhibition of autocrine fibroblast growth factor signaling by the adenovirus-mediated expression of an antisense trangene or a dominant negative receptor in human glioma cells in vitro"Int J Oncol. 21. 629-636 (2002)
• [文献書誌] Ueda S, Kato S, Matsuoka H, Kimoto M, Okuda S, Morimatsu M, Imaizumi T.: "Regulation of cytokine-induced Nitric Oxide Synthesis by Asymmetric Dimethylarginie : Role of Dimethylarginine Dimethylaminohydrolase"Circ Res. 92. 226-233 (2003)
• [文献書誌] Shibata R, Kai H, Seki Y, Kato S, Wada Y, Hanakawa Y, Hashimoto K, Yoshimura A, Imaizumi T.: "Inhibition of STAT3 prevents neointima formation by inhibiting proliferation and promoting apoptosis of neointimal smooth muscle cells"Hum Gene Ther. (in print).
• [文献書誌] Rei Shibata, Hisashi Kai, Yukihiko Seki, Seiya Kato, Minoru Morimatsu, Kozo Kaibuchi, Tutomu Imaizumi.: "Role of Rho-associated protein kinase in neointima formation after vascular injury"Circulation. 103・2. 284-289 (2001)
• [文献書誌] Seiya Kato, Seiji Ueda, Kiyoshi Tamaki, Makiko Fujii, Kohei Miyazono, Peter ten Dijke, Minoru Morimatsu, Seiya Okuda.: "Ectopic expression of Smad7 inhibits transforming growth factor-β responses in vascular smooth muscle cells"Life Sci. 69・22. 2641-2652 (2001)
• [文献書誌] Yoshihiro Wada, Seiya Kato, Kenichi Okamoto, Shinsuke Izumant, Shigeaki Aoyagi, Minoru Morimatsu.: "Diltiazem, a calcium antagonist, inhibits matrix metalloproteinase-1 (tissue collagenase) production and collagenolytic activity in human vascular smooth muscle cells"Int J Mol Med. 8. 561-566 (2001)
• [文献書誌] Toshikatsu hanada, Takafumi Yoshida, Ichiko Kinjo, Shigeru Minoguchi, Hideo Yasukawa, Seiya Kato, Hiromitsu Mimata, Yoshio Nomura, Youichi Seki, Masato Kubo, Akihiko Yoshimura.: "A mutant form of JAB/SOCS1 augments the cytokine-induced JAK/STAT pathway by accelerating degradation of wild-type JAB/CIS family proteins through the SOCS-box"J Biol Chem. 276・44. 40746-40754 (2001)
• [文献書誌] Teruhiko Fujii, Seiya Kato, Hideaki Yamana, Yuichi Tanaka, Hiromasa Fujita, Kazuo Shirouzu, Minoru Moorimatsu: "Expression of G1 cell cycle markers and the effect of adenovirus-mediated overexpression of p21 Waf-1 in squamous cell carcinoma of the esophagus"Int J Oncol. 18. 157-163 (2001)
• [文献書誌] Zemmyo N, Komiya S, Hamada T, Miraoka K, Kato S, Fujii T, Yano H, Irie K, Nagata K.: "Transcriptional activation of p21 by vitamine D3 or vitamine K2 leads to differentiation of p53-deficient MG-63 osteosarcoma cells"Hum Pathol. 32・4. 410-416 (2001)