2002 Fiscal Year Annual Research Report

神経芽腫における自然消退モデルの確立とその分子機構

Research Project

Project/Area Number	14570164
Research Institution	National Research Institute for Child Health and Development
Principal Investigator	秦順一国立成育医療センター研究所, 所長 (90051614)
Co-Investigator(Kenkyū-buntansha)	山田健人慶應義塾大学, 医学部, 講師 (60230463) 松岡健太郎国立成育医療センター病院, 医員 (90286443)
Keywords	神経芽腫 / シュワン細胞 / 神経冠細胞 / EGFP / レトロウィルスベクター / S-100
Research Abstract	本研究は、神経芽腫の生物学的特異性、特に腫瘍細胞の分化・成熟能と間質細胞であるシュワン細胞の起源とその分化および本腫瘍の自然消退のメカニズムを分子レベルで解明するため企図された。神経芽腫の間質であるシュワン細胞の由来については、腫瘍細胞である神経冠細胞を起源とする説および腫瘍局所の未熟間葉系細胞からリクルートされるという説があり、未だ定説とはなっていない。そこで本年度はこれらシュワン細こ胞の起源について明らかにした。本年度得られた成果は以下のごとくである。神経芽腫組織へのヒト骨髄間質細胞の導入による、間質細胞の形質変化についてヒト骨髄間質細胞へマーカー遺伝子EGFPを有する高効率レトロウイルスベクターMSGFPを感染・導入した。さらに、これらEGFP導入骨髄間質細胞をNOD/SCIDマウスへ移植し、定着したヒト神経芽腫組織内に注入した。導入したヒト骨髄間質細胞の形質変化およびその局在を検討するため、EGFPの同定およびシュワン細胞に特異的なS100抗体を用いて同時に観察した。その結果、EGFP陽性細胞は神経芽腫組織内に認められ、これらは同時にS100抗体陽性であった。以上の結果から、神経芽腫の間質成分であるシュワン細胞は神経冠細胞由来の腫瘍細胞から分化するのではなく、腫瘍周辺の間質が分化することによって生じることが明らかとなった。

Research Products

(20 results)

All Other

All Publications (20 results)

[Publications] yabe, H., Fukuma, M., Urano, F., Yashida, K., Kato, S., Hata, J.et al.: "Lack of matrix metalloproteinase (MMP)-1 and -3expression in Ewing saarcoma may be due to loss of accessibility of the MMP regulatory element to the specific fusion protein in vivo"BBRC. 293. 61-71 (2002)
[Publications] Ambros, IM., Hata, J., Joshi, VV., Roald, B., Dehner, LP., Tuchler, H.et al.: "Morphologic Features of Neuroblastoma (Schwannian Stroma-Poor Tumors) in Clinic ally Favorable and Unfavorable Groups"cancer. 94. 1574-1583 (2002)
[Publications] Fukuzawa, A., Sakamoto, J., Heathcott, RW., Hata, J.: "A necropsy case of Denys-Drash syndrome with a WT1 mutation in exon 7"J Med Genet. 39. 48-52 (2002)
[Publications] Ikeda, H., lehara, T., Tsuchida, Y., Kaneko, M., Hata.J.et al.: "Experience with International Neuroblastoma Staging System and Pathology Classi fication"Brit J Cancer. 86. 1110-1116 (2002)
[Publications] Nishimori, H., Sasaki, Y., Yoshida, K., Irifune, H., Hata, J.et al.: "The Id2 gene is a novel target of transcriptional activation by EMS-ETS fusion proteins in Ewing family tumors"Oncogene. 21. 8302-8309 (2002)
[Publications] Shibata, R., Hashiguchi, A., Sakamoto J., Umezawa, A., Hata, J.: "Correlation between a specific Wilms tumor suppressor gene(WT1)mutation and the histological findings in Wilms tumor(WT1)"J Med Genet. 39. e83-e87 (2002)
[Publications] Inoshita, S., Takeda, K., Hatai, K., Sano, Y., Hata, J.: "Phosshorylation and Inactivation of Mcl-1 by c-Jun N-teminal Kinase (JNK) in Response to Oxidative Stress"JBC. 277. 43730-43734 (2002)
[Publications] Fukuma, M., Hata, J., Umezawa, A.: "Id2 is a target of the EWS/ets chimeric protein in Ewing sarcoma family"Oncogene. 22. 1-9 (2003)
[Publications] fukuma, M., Abe, H., Okita, H., Yamada T., Hata, J.: "Monoclonal antibody,4C4-mAb, specifically recognizes keratan sulfate proteog lycan on human embryonal carcinoma cells"J Pathol. (in press). (2003)
[Publications] Fukuzawa, R., Eccles, MR., Ikeda, M., Hata, J.: "Embryonal hyperplasia of Bowmann's capsular epithelium in patients with WT1 mutat ions"Pediatr Nephrol. 18. 9-13 (2003)
[Publications] Shibata, R., Umezawa, A., Takehara, K., Aoki, D., Nozawa.S., Hata, J.: "Primary carcinosarcoma of the vagina"Pathol Int. 53. 40-44 (2003)
[Publications] Shibata, R., Takata, A., Hashiguchi, A., Umezawa, A., Yamada, T., Hata, J.: "Responsiveness of chemotherapy based on the histologocal type and Wilms' tumor suppressor gene mutation in bilateral Wilms' tumor"Pathol Int. 53. 214-220 (2003)
[Publications] Tsunoda, K., Ota, T., Aoki, M., Yamada, T., Nagai, T., Nakagawa, T.et al.: "Induction of pemphigus phenotype by a monoclonal antibody against the amino-terminal adhesive interface of desmoglein 3"J Immunology. 170. 2170-2178 (2003)
[Publications] Yuasa, H., Takakura, N., Shimomura, T., Suenobu, S., Yamada, T.et al.: "Analysis of human TIE2 function on hematopoietic stem cells in umbilical cord blood"BBRC. 298. 731-737 (2002)
[Publications] Nishimura, N., Nakayama, T., Tonoike, H., Yamada, T.et al.: "Various amplification of direct PCR using Blood Samples"Clinical Laboratory. 48. 377-384 (2002)
[Publications] Kakimoto, T., Hattori, Y., Okamoto, S., Yamada, T.et al.: "Thalidomide for the Treatment of Refractory Multiple Myeloma: Association of Plasma Concentrations of Thalidomide and Angiogenic Growth Factors with Clinical Outcome"Jpn J Cancer Res. 93. 1029-1036 (2002)
[Publications] Zhao, C., Hashiguchi, A., Kondoh, K., Du W., Hata, J., Yamada, T.: "Exogenous expression of heat shock protein 90kDa retards the cell cycle and impairs the heat shock response"Experimental Cellular Research. 275. 200-214 (2002)
[Publications] Sato, N., Hattori, Y., Du W., Yamada, T., Kamata, T.et al.: "Elevated level of basic fibroblast growth factor in multiple myeloma correlates with increased disease activity"Jpn J Cancer Res. 93. 459-466 (2002)
[Publications] Yamaoka, T., Yoshida, K., Yamada, T., Yano, M., Matsui, T., Hata, J.et al.: "Transgenic expression of FGF8 and FGF10 induces transdifferntiation of panceratic islet cells into hepatocytes and exocrine cells"BBRC. 292. 138-143 (2002)
[Publications] Fukao, T., Yamada, T., Tanabe, M., Terauchi, Y., Hata, J.et al.: "Selective loss of gastrointestinal mast cells and impaired immunity to intestinal parasites in Pik3r1 deficient mice"Nature Immunology. 3. 295-304 (2002)

2002 Fiscal Year Annual Research Report

神経芽腫における自然消退モデルの確立とその分子機構

Principal Investigator

秦 順一 国立成育医療センター研究所, 所長 (90051614)

Research Products

[Publications] yabe, H., Fukuma, M., Urano, F., Yashida, K., Kato, S., Hata, J.et al.: "Lack of matrix metalloproteinase (MMP)-1 and -3expression in Ewing saarcoma may be due to loss of accessibility of the MMP regulatory element to the specific fusion protein in vivo"BBRC. 293. 61-71 (2002)

[Publications] Ambros, IM., Hata, J., Joshi, VV., Roald, B., Dehner, LP., Tuchler, H.et al.: "Morphologic Features of Neuroblastoma (Schwannian Stroma-Poor Tumors) in Clinic ally Favorable and Unfavorable Groups"cancer. 94. 1574-1583 (2002)

[Publications] Fukuzawa, A., Sakamoto, J., Heathcott, RW., Hata, J.: "A necropsy case of Denys-Drash syndrome with a WT1 mutation in exon 7"J Med Genet. 39. 48-52 (2002)

[Publications] Ikeda, H., lehara, T., Tsuchida, Y., Kaneko, M., Hata.J.et al.: "Experience with International Neuroblastoma Staging System and Pathology Classi fication"Brit J Cancer. 86. 1110-1116 (2002)

[Publications] Nishimori, H., Sasaki, Y., Yoshida, K., Irifune, H., Hata, J.et al.: "The Id2 gene is a novel target of transcriptional activation by EMS-ETS fusion proteins in Ewing family tumors"Oncogene. 21. 8302-8309 (2002)

[Publications] Shibata, R., Hashiguchi, A., Sakamoto J., Umezawa, A., Hata, J.: "Correlation between a specific Wilms tumor suppressor gene(WT1)mutation and the histological findings in Wilms tumor(WT1)"J Med Genet. 39. e83-e87 (2002)

[Publications] Inoshita, S., Takeda, K., Hatai, K., Sano, Y., Hata, J.: "Phosshorylation and Inactivation of Mcl-1 by c-Jun N-teminal Kinase (JNK) in Response to Oxidative Stress"JBC. 277. 43730-43734 (2002)

[Publications] Fukuma, M., Hata, J., Umezawa, A.: "Id2 is a target of the EWS/ets chimeric protein in Ewing sarcoma family"Oncogene. 22. 1-9 (2003)

[Publications] fukuma, M., Abe, H., Okita, H., Yamada T., Hata, J.: "Monoclonal antibody,4C4-mAb, specifically recognizes keratan sulfate proteog lycan on human embryonal carcinoma cells"J Pathol. (in press). (2003)

[Publications] Fukuzawa, R., Eccles, MR., Ikeda, M., Hata, J.: "Embryonal hyperplasia of Bowmann's capsular epithelium in patients with WT1 mutat ions"Pediatr Nephrol. 18. 9-13 (2003)

[Publications] Shibata, R., Umezawa, A., Takehara, K., Aoki, D., Nozawa.S., Hata, J.: "Primary carcinosarcoma of the vagina"Pathol Int. 53. 40-44 (2003)

[Publications] Shibata, R., Takata, A., Hashiguchi, A., Umezawa, A., Yamada, T., Hata, J.: "Responsiveness of chemotherapy based on the histologocal type and Wilms' tumor suppressor gene mutation in bilateral Wilms' tumor"Pathol Int. 53. 214-220 (2003)

[Publications] Tsunoda, K., Ota, T., Aoki, M., Yamada, T., Nagai, T., Nakagawa, T.et al.: "Induction of pemphigus phenotype by a monoclonal antibody against the amino-terminal adhesive interface of desmoglein 3"J Immunology. 170. 2170-2178 (2003)

[Publications] Yuasa, H., Takakura, N., Shimomura, T., Suenobu, S., Yamada, T.et al.: "Analysis of human TIE2 function on hematopoietic stem cells in umbilical cord blood"BBRC. 298. 731-737 (2002)

[Publications] Nishimura, N., Nakayama, T., Tonoike, H., Yamada, T.et al.: "Various amplification of direct PCR using Blood Samples"Clinical Laboratory. 48. 377-384 (2002)

[Publications] Kakimoto, T., Hattori, Y., Okamoto, S., Yamada, T.et al.: "Thalidomide for the Treatment of Refractory Multiple Myeloma: Association of Plasma Concentrations of Thalidomide and Angiogenic Growth Factors with Clinical Outcome"Jpn J Cancer Res. 93. 1029-1036 (2002)

[Publications] Zhao, C., Hashiguchi, A., Kondoh, K., Du W., Hata, J., Yamada, T.: "Exogenous expression of heat shock protein 90kDa retards the cell cycle and impairs the heat shock response"Experimental Cellular Research. 275. 200-214 (2002)

[Publications] Sato, N., Hattori, Y., Du W., Yamada, T., Kamata, T.et al.: "Elevated level of basic fibroblast growth factor in multiple myeloma correlates with increased disease activity"Jpn J Cancer Res. 93. 459-466 (2002)

[Publications] Yamaoka, T., Yoshida, K., Yamada, T., Yano, M., Matsui, T., Hata, J.et al.: "Transgenic expression of FGF8 and FGF10 induces transdifferntiation of panceratic islet cells into hepatocytes and exocrine cells"BBRC. 292. 138-143 (2002)

[Publications] Fukao, T., Yamada, T., Tanabe, M., Terauchi, Y., Hata, J.et al.: "Selective loss of gastrointestinal mast cells and impaired immunity to intestinal parasites in Pik3r1 deficient mice"Nature Immunology. 3. 295-304 (2002)

秦順一国立成育医療センター研究所, 所長 (90051614)