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2000 Fiscal Year Final Research Report Summary

Ultrastructural and cytochemical studies on cancer and apoptosis in bone.

Research Project

Project/Area Number 09557164
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field Surgical dentistry
Research InstitutionNIIGATA UNIVERSITY

Principal Investigator

SHINGAKI Susumu  Faculty of Dentistry Associate Professor, 歯学部, 助教授 (30134943)

Co-Investigator(Kenkyū-buntansha) ITO Masahiro  Niigata University Faculty of Dentistry Assistant, 歯学部, 助手 (40313522)
TAKADA Masahito  Niigata University Faculty of Dentistry Assistant, 歯学部, 助手 (10251828)
Project Period (FY) 1997 – 2000
Keywordsbone metastasis / bone invasion / osteoclasts / bisphosphonates / apoptosis / ALPase / immunohistochemistry / morphology
Research Abstract

We examined the mechanisms of bone metastasis and bone invasion. The tumor mass was surrounded by a membrane consisting of fibroblastic cells. These cells were positive for ALP ase. TRAPase-positive cells were localized close to the ALP ase-positive cells and numerous osteoclasts were observed on the neighboring bone surfaces. It seems that PTHrP secreted by the tumor cells appears to stimulate differentiation of osteoclasts and bone resorption in a paracrine manner through PTH/PTHrP receptor-immunopositive osteoblastic cells. In bone metastatic, breast cancer cells produced VEGF and induced many CD31-positive blood vessels in bone. TRAPase-positive osteoclasts directly contacted to RANKL-positive cells. It seems that VEGF of the tumor cells induce growth of cancer and osteoclasts progenitor, and stimulate differentiation and activation of osteoclasts via RANKL of osteoblastic cells. Furthermore, we found that bisphosphonate inhibited the number of osteoclasts and blood vessels in bone metastatic area. We investigated the mechanism which a mutant ALPase induced bone disease in vitro. The mutant ALPase gene resulted in protein synthesis but not ER-to-Golgi apparatus trafficking. Then, osteoclasts apoptosis were studied in the tibia of rats treated with a bisphosphonate. They became devoid of ruffled borders and detached from bone surface, and showed formation of many vesicles and degradation of Golgi apparatus and DNA fragmentation. The majority of them are eliminated by macrophages, but there are some that escape into blood vessels. Furthermore, we found that bisphosphonates directly affect osteoclasts without mediating its deposition to the bone matrix.

  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Ito, M.: "Bisphosphonate acts on osteoclasts independent of ruffled borders in osteosclerotic (oc/oc) mice."Bone.. 28(in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 伊藤将広: "Bisphosphonatesの作用機序"THE BONE.. 7(in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fukushi-Irie, M.: "Possible interference between tissue-non-specific alkaline phosphatase with an Arg54→Cys substitution and a counterpart with an Asp277→Ala substituion found in a compound heterozygote associated with severe hypophosphatasia."Biochem. Journal.. 348. 633-642 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 伊藤将広: "破骨細胞の細胞死"THE BONE.. 14. 3-6 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 網塚憲生: "骨転移に関わる細胞群"ホルモンと臨床. 7. 585-594 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ito, M.: "Ultrastructural and cytochemical studies on cell death of osteoclasts induced by bisphosphonate treatment."Bone.. 25. 447-452 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 伊藤将広: "骨腫瘍と骨組織"Quintessence.. 18. 183-190 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 織田公光: "低ホスファターゼ症"Niigata Dental Journal.. 29. 35-36 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ono, Y.: "Clinicopathologic significance of laminin-5 gamma2 chain expression in squamous cell carcinoma of the tongue. immunohistochemical analysis of 67 lesion."Cancer.. 85. 2315-2321 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ito, M.: "Ultrastructural and cytochemical studies on cell death of osteoclasts."Niigata Dental Journal.. 28. 87-88 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mahmood, J. U.: "Heterogeneity of squamous cell carcinomas of the head and neck in relation to clinicopathological parameters."Br. J. Oral. Maxillofac. Surg.. 36. 446-452 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiraga, T.: "Morphology of bone metastasis."Eur. J. Cancer.. 34. 230-239 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Naito, Y.: "Effects of UFT on metastatic potentials of hamster squamous cell carcinoma (O-1N)."Oral Oncology.. 34. 326-331 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ono, Y.: "Vascular invasion of O-1N, hamster squamous cell carcinoma with high potential of lymph node metastasis. ultrastructural comparision between lymphatics and blood vessels."Path. Int.. 8. 254-264 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 網塚憲生: "骨と軟骨組織におけるアポトーシス"現代医療. 29. 171-180 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shingaki, S.: "Impact of clinicopathologic parameters on survival of patients with tongue carcinoma."Asian J. Oral Maxillofac. Surg.. 9. 107-116 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中島民雄: "癌の転移"Niigata Dental Journal.. 27. 1-12 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ito, M., et al.: "Bisphosphonate acts on osteoclasts independent of ruffled borders in osteosclerotic(oc/oc)mice."Bone.. 28, (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito, M., et al.: "Mechanism of action of bisphosphonates."THE BONE.. 7, (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukushi-Irie, M.: "Possible interference between tissue-non-specific alkaline phosphatase with an Arg54 -->Cys substitution and a counterpart with an Asp277 -->Ala substitution found in a compound heterozygote associated with severe hypophosphatasia."Biochme.Journal.. 348. 633-642 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito, M., et al.: "Apoptosis of osteoclasts."THE BONE.. 14. 3-6 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Amizuka, N., et al.: "Cellular involvement in bone metastasis."Hormone to Rinsho.. 7. 585-594 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito, M., et al.: "Ultrastructural and cytochemical studies on cell death of osteoclasts induced by bisphosphonate treatment."Bone.. 25. 447-452 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito, M., et al.: "Tumor and bone"Quinitessence.. 18. 183-190 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Oda, K., et al.: "Hypophosphatasia."Niitgata Dental Journal.. 29. 35-36 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ono, Y., et al.: "Clinicopathologic significance of laminin-5 gamma2 chain expression in squamous cell carcinoma of the tongue. immunohistochemical analysis of 67 lesion."Cancer.. 85. 2315-2321 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito, M., et al.: "Ultrastructural and and cytochemical studies on cell death of osteoclasts."Niigata dental Journal.. 28. 87-88 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mahmood, J.U., et al.: "Heterogeneity of squamous cell carcinomas of the head and neck in relation to clinicopathological parameters."Br.J.Oral Maxillofac.Surg.. 36. 446-452 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiraga, T., et al.: "Morphology of bone metastasis."Eur.J.Cancer.. 34. 230-239 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Naito, Y., et al.: "Effects of UFT on metastatic potentials of hamster squamous cell carcinoma(O-1N)"Oral Oncology.. 34. 326-331 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ono, Y., et al.: "Vascular invasion of O-1N, hamster squamous cell carcinoma with high potential of lymph node metastasis. ultrastructural comparison between lymphatics and blood vessels."Path.Int.. 8. 254-264 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Amizuka, N., et al.: "Apoptosis in bone."Gendai-iryo.. 29. 171-180 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shingaki, S., et al.: "Impact of clinicopathologic parameters on survival of patients with tongue carcinoma."Asian J.Oral Maxillofac.Surg.. 9. 107-116 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakajima, T., et al.: "Metastasis of cancer."Niigata dental Journal.. 27. 1-12 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2002-03-26  

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