2002 Fiscal Year Annual Research Report

αvβ3インテグリン結合分子の骨転移癌のアポトーシス・接着制御機能の解析

Research Project

Project/Area Number	14028022
Research Institution	Tokyo Medical and Dental University
Principal Investigator	野田政樹東京医科歯科大学, 難治疾患研究所, 教授 (50231725)
Co-Investigator(Kenkyū-buntansha)	辻邦和東京医科歯科大学, 難治疾患研究所, 助手 (20323694) 二藤彰東京医科歯科大学, 難治疾患研究所, 助教授 (00240747)
Keywords	オステオポンチン / 転移 / 悪性黒色腫 / 血管形成 / 固形癌 / ノックアウトマウス
Research Abstract	オステオポンチンは腫瘍の転移における乳癌の予後との相関が報告され、また血中のオステオポンチンレベルが前立腺癌の予後との相関を持つことが臨床的に明らかにされたが、なおその癌の転移とオステオポンチンレベルの相関性をつなぐメカニズムについては明らかでない。今回の研究においては癌の転移巣における血管形成とオステオポンチンの役割についての検索を行った。すなわち、静脈より導入した悪性黒色腫細胞が転移する肺における転移巣の数がオステオポンチンの欠失により抑制されるモデルを用い、その転移巣の周囲の血管組織を形態学的に観察したところ腫瘍の転移巣周辺の血管組織の形成においては野生型とオステオポンチンのノックアウトマウスはほぼ同様であった。B16悪性黒色腫細胞とこの細胞が誘導する可能性のある血管形成におけるオステオポンチンの役割を明らかにするためにB16悪性黒色腫を皮内に投与し、約1cm直径の腫瘍塊を形成させる実験を行ったところ、野生型ならびにオステオポンチン欠失マウスともに同様の大きさの腫瘍塊の形成が観察され血管形成の検索を行った結果、両遺伝子型で同様の血管の形成が観察された。一方、炎症による血管形成モデルについてはオステオポンチンの欠失によって抑制が観察された。以上の結果は腫瘍の転移の形成の際に起こる血管形成や腫瘍が局所で腫瘍塊を形成して固形癌としての増大する際の血管形成についてはオステオポンチンが関与しないメカニズムが存在し、この分子の癌の転移における作用点は転移先の腫瘍形成以前の段階、即ち血管からの遊走や血管内への着床の段階にあることが推察された。

Research Products

(12 results)

All Other

All Publications (12 results)

[Publications] Shen ZJ: "Negative Regulation of Bone Morphogenetic Protein/Smad Signaling by Cas-interacting Zinc Finger Protein in Osteoblasts"The Journal of Biological Chemistry. 27. 29840-29846 (2002)
[Publications] Yumoto K: "Osteopontin deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice"Proceeding of the National Academy of Sciences USA. 99. 4556-4561 (2002)
[Publications] Usui M: "Enhancing effect of Tob deficiency on bone formation is specific to BMP-induced osteogenesis"Journal of Bone and Mineral Research. 17. 1026-1033 (2002)
[Publications] Kitahara K: "Osteopontin-Denficiency Induces Parathyroid Hormone Enhancement of Cortical Bone Formation"Endocrinology. (in press). (2003)
[Publications] Ishijima M: "Resistance to unloading-induced three-dimensional bone loss in osteopontin-deficient mice"Journal of Bone and Mineral Research. 17. 661-667 (2002)
[Publications] Salingcarnboriboon R: "Establishment of Tendon-Derived Cell Lines Exhibiting Pluripotent Mesenchymal Stem Cell-Like Property"Experimental Cell Research. (in press). (2003)
[Publications] Maeda Y: "Coordinated development of embryonic long bone in ovo organ culture on chorioallantoic membrane prevents perichondrium-derived suppressive signals against cartilage growth"Bone. 32(1). 27-34 (2002)
[Publications] Yagi K: "Bone Morphogenetic Protein-2 Enhances Osterix Gene Expression in Chondrocytes"Journal of Cellular Biochemistry. 88. 1077-1083 (2003)
[Publications] Yoshikawa M: "CLC-3 deficiency leads to phoenotypes similar to human neuronal ceroid lipofuscinosis"Genes to Cell. 7. 597-605 (2002)
[Publications] Yamashita T: "Double Mutation in Klotho and Osteoprotegenin Gene Loci Rescued Osteopetronic Phenotype"Endocrinology. 143. 4711-4717 (2002)
[Publications] Morinobu M: "Osteopontin Expression in Osteoblasts and Osteocytes during Bone Formation under Mechanical Stress in the Calvarial in Vivo"Journal of Bone and Mineral Research. (in press). (2003)
[Publications] Kashimada K: "Defects in growth and bone metabolism in klotho mutant mice are resistant to GH treatment"J. Endocrinology. 174. 403-410 (2002)

2002 Fiscal Year Annual Research Report

αvβ3インテグリン結合分子の骨転移癌のアポトーシス・接着制御機能の解析

Principal Investigator

野田 政樹 東京医科歯科大学, 難治疾患研究所, 教授 (50231725)

Research Products

[Publications] Shen ZJ: "Negative Regulation of Bone Morphogenetic Protein/Smad Signaling by Cas-interacting Zinc Finger Protein in Osteoblasts"The Journal of Biological Chemistry. 27. 29840-29846 (2002)

[Publications] Yumoto K: "Osteopontin deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice"Proceeding of the National Academy of Sciences USA. 99. 4556-4561 (2002)

[Publications] Usui M: "Enhancing effect of Tob deficiency on bone formation is specific to BMP-induced osteogenesis"Journal of Bone and Mineral Research. 17. 1026-1033 (2002)

[Publications] Kitahara K: "Osteopontin-Denficiency Induces Parathyroid Hormone Enhancement of Cortical Bone Formation"Endocrinology. (in press). (2003)

[Publications] Ishijima M: "Resistance to unloading-induced three-dimensional bone loss in osteopontin-deficient mice"Journal of Bone and Mineral Research. 17. 661-667 (2002)

[Publications] Salingcarnboriboon R: "Establishment of Tendon-Derived Cell Lines Exhibiting Pluripotent Mesenchymal Stem Cell-Like Property"Experimental Cell Research. (in press). (2003)

[Publications] Maeda Y: "Coordinated development of embryonic long bone in ovo organ culture on chorioallantoic membrane prevents perichondrium-derived suppressive signals against cartilage growth"Bone. 32(1). 27-34 (2002)

[Publications] Yagi K: "Bone Morphogenetic Protein-2 Enhances Osterix Gene Expression in Chondrocytes"Journal of Cellular Biochemistry. 88. 1077-1083 (2003)

[Publications] Yoshikawa M: "CLC-3 deficiency leads to phoenotypes similar to human neuronal ceroid lipofuscinosis"Genes to Cell. 7. 597-605 (2002)

[Publications] Yamashita T: "Double Mutation in Klotho and Osteoprotegenin Gene Loci Rescued Osteopetronic Phenotype"Endocrinology. 143. 4711-4717 (2002)

[Publications] Morinobu M: "Osteopontin Expression in Osteoblasts and Osteocytes during Bone Formation under Mechanical Stress in the Calvarial in Vivo"Journal of Bone and Mineral Research. (in press). (2003)

[Publications] Kashimada K: "Defects in growth and bone metabolism in klotho mutant mice are resistant to GH treatment"J. Endocrinology. 174. 403-410 (2002)

野田政樹東京医科歯科大学, 難治疾患研究所, 教授 (50231725)