1989 Fiscal Year Annual Research Report

癌胎児性抗原(CEA)の癌特異性の本態の解明

Research Project

Project/Area Number	01015113
Research Institution	Fukuoka University
Principal Investigator	松岡雄治福岡大学, 医学部, 教授 (70078773)
Co-Investigator(Kenkyū-buntansha)	白日高歩福岡大学, 医学部, 助教授 (20038863) 山本博福岡大学, 医学部, 助教授 (70099018) 黒木求福岡大学, 医学部, 助手 (10131822) 黒木政秀福岡大学, 医学部, 助教授 (40122692) 池原征夫福岡大学, 医学部, 教授 (70037612)
Keywords	癌胎児性抗原 / CEA / glycolipid anchor / 正常糞便抗原 / 癌特異的抗原性 / 正常大腸粘膜のCEA産生
Research Abstract	最近我々は正常大腸粘膜のCEA含量は従来の報告通り極く少量であるが、それをorgan cultureすると癌組織と同等かそれ以上にCEAを産生することを見出し、CEAの癌特異性の本態は正常粘膜と癌組織の間にみられるCEAの移送・放出機序の違いに求めねばならないと考え検討した。本年度次の知見を得た。(1)正常人の1日排便量(200〜250g)中に50〜70mgものCEAが存在する。(2)その約10%は新鮮糞便中で既に可溶化されている(自然可溶化抗原)。あとの90%以上はglycolipidを介して膜に結合して存在し、phosphatidylinositol specific phospholipase C(PIーPLC)により遊離される(PIーPLC可溶化抗原)。(3)従来正常糞便抗原(NFA)と同定されていたものは自然可溶化抗原であり、PIーPIC可溶化抗原の抗原性は癌組織のCEAと類似する。(4)これまでNFAとの比較から癌組織のCEAに特異的と考えられていた抗原性はCEA分子のC端部にglycosylinositol phosphate(GIP)の結合により生ずる抗原活性と考えられる。正常人の1日の排便量中に50〜70mgもの大量のCEAが存在することは、正常大腸粘膜でCEAが活発に産生されるという我々の知見を強く支持する所見である。しかもそれが膜結合型抗原として糞便中に存在するという新しい知見は、CEAの癌特異性の本態を単に上皮細胞から移送・放出機序に求めるのではなく、粘膜上皮細胞の増殖、分化、移動及び脱落の過程に求めねばならないという今後の新しい研究課題が生じたことになる。一方、我々が最近報告したごとく、CEAの癌特異的抗原活性と考えられていたGIPー依存性の抗原性をより強く認識するCEA測定系は腫瘍マーカーとしてのCEAの癌特異性、感受性及び精度を明確に向上させるので、血中に放出されるCEA分子上のGIPの有無がマーカーとしての有用性に大きく寄与しているらしい。従って癌細胞からどのような機序によりCEA分子が血中に放出されるかも今後解明すべき重要な研究課題となった。

Research Products

(15 results)

All Other

All Publications (15 results)

[Publications] Hammarstrom,S.: "Antigenic sites in carcinoembryonic antigen." Cancer Res.49. 4852-4858 (1989)
[Publications] Oikawa,S.: "A pregnancyーspecific beta1ーglycoprotein,a CEA gene family member,expressed in a human promyelocytic leukemia cell line,HLー60:structures of protein,mRNA and gene." Biochem.Biophys.Res.Commun.163. 1021-1031 (1989)
[Publications] Watanabe,Y.: "Effect of tumor mass and antigenic nature of the biodistribution of labeled monoclonal antibodies in mice." Cancer Res.49. 2884-2889 (1989)
[Publications] Ohbayashi,H.: "Novel methods to determine the epitopes on the asparagineーlinked oligosaccharides of glycoproteins." Anal.Biochem.182. 200-206 (1989)
[Publications] Oikawa,S.: "Cell adhesion activity of nonーspecific crossーreacting antigen(NCA)and carcinoembryonic antigen(CEA)expressed on CHO cell surface;homophilic and heterophilic adhesion." Biochem.Biophys.Res.Commn.164. 39-45 (1989)
[Publications] Yamashita,K.: "Carbohydrate structures of NCAー2,a glycoprotein purified from meconium as an antigen crossーreacting with antiーCEA antibody:Occurrence of complexーtype sugar chains with the Gal beta1→3GlcNAcbeta1→3Galbeta1→4GlcNAbeta1→outer chains." J.Biol.Chem.264. 17873-17881 (1989)
[Publications] Kuroki,Mo.: "A novel CEAーcrossーreacting antigen of molecular weight 140,000 expressed on human lymphoid cell lines." Molecular lmmunology.
[Publications] Kuroki,Mo.: "Nonspecific crossーreacting antigen(NCA)expressed by human granulocytes:six species with different peptide sizes and membrane anchoring forms." Biochem.Biophys.Res.Commun.
[Publications] Arakawa,F.: "Characterization of a cDNA clone encoding a new species of the nonspecific crossーreacting antigen(NCA),a member of the CEA gene family." Biochem.Biophys.Res.Commun.
[Publications] Arakawa,F.: "The nucleotide and deduced amino acid sequences of a cDNA encoding a new species of pregnancyーspecific beta1ーglycoprotein(PSbetaG)." Biochem.Biophys.Acta.
[Publications] Matsuoka,Y.: "Characterization of carcinoembryonic antigenーrelatid antigens in normal adult feces." Jpn.J.Cancer Res.
[Publications] Watanabe,Y.: "Influence of cocktails of labeled monoclonal antibodies on the localization of antibodies in human tumor xenografts." Jpn.J.Cancer Res.
[Publications] Kobata,A.: "Comparative study of the sugar chains of carcinoembryonic antigen and its crossreacting antigen purified from meconium.In The Carcinoembryonic Antigen Gene Family." Elsevier,Amsterdam, 136 (1989)
[Publications] Matsuoka,Y.: "Membrane anchoring of carcinoembryonic antigen and demonstration of its active production in normal colon mucosa. In The Carcinoembryonic Antigen Gene Family." Elsevir,Amsterdam, 136 (1989)
[Publications] Nakazato,H.: "Gene and deduced primary structures of pregnancyーspecific beta1ーglycoproteins subfamily members within CEA family within immunoglobulin superfamily.In The Carcinoembryonic Antigen Gene Family." Elsevier,Amsterdam, 136 (1989)

1989 Fiscal Year Annual Research Report

癌胎児性抗原(CEA)の癌特異性の本態の解明

Principal Investigator

松岡 雄治 福岡大学, 医学部, 教授 (70078773)

Research Products

[Publications] Hammarstrom,S.: "Antigenic sites in carcinoembryonic antigen." Cancer Res.49. 4852-4858 (1989)

[Publications] Oikawa,S.: "A pregnancyーspecific beta1ーglycoprotein,a CEA gene family member,expressed in a human promyelocytic leukemia cell line,HLー60:structures of protein,mRNA and gene." Biochem.Biophys.Res.Commun.163. 1021-1031 (1989)

[Publications] Watanabe,Y.: "Effect of tumor mass and antigenic nature of the biodistribution of labeled monoclonal antibodies in mice." Cancer Res.49. 2884-2889 (1989)

[Publications] Ohbayashi,H.: "Novel methods to determine the epitopes on the asparagineーlinked oligosaccharides of glycoproteins." Anal.Biochem.182. 200-206 (1989)

[Publications] Oikawa,S.: "Cell adhesion activity of nonーspecific crossーreacting antigen(NCA)and carcinoembryonic antigen(CEA)expressed on CHO cell surface;homophilic and heterophilic adhesion." Biochem.Biophys.Res.Commn.164. 39-45 (1989)

[Publications] Kuroki,Mo.: "A novel CEAーcrossーreacting antigen of molecular weight 140,000 expressed on human lymphoid cell lines." Molecular lmmunology.

[Publications] Kuroki,Mo.: "Nonspecific crossーreacting antigen(NCA)expressed by human granulocytes:six species with different peptide sizes and membrane anchoring forms." Biochem.Biophys.Res.Commun.

[Publications] Arakawa,F.: "Characterization of a cDNA clone encoding a new species of the nonspecific crossーreacting antigen(NCA),a member of the CEA gene family." Biochem.Biophys.Res.Commun.

[Publications] Arakawa,F.: "The nucleotide and deduced amino acid sequences of a cDNA encoding a new species of pregnancyーspecific beta1ーglycoprotein(PSbetaG)." Biochem.Biophys.Acta.

[Publications] Matsuoka,Y.: "Characterization of carcinoembryonic antigenーrelatid antigens in normal adult feces." Jpn.J.Cancer Res.

[Publications] Watanabe,Y.: "Influence of cocktails of labeled monoclonal antibodies on the localization of antibodies in human tumor xenografts." Jpn.J.Cancer Res.

[Publications] Kobata,A.: "Comparative study of the sugar chains of carcinoembryonic antigen and its crossreacting antigen purified from meconium.In The Carcinoembryonic Antigen Gene Family." Elsevier,Amsterdam, 136 (1989)

[Publications] Matsuoka,Y.: "Membrane anchoring of carcinoembryonic antigen and demonstration of its active production in normal colon mucosa. In The Carcinoembryonic Antigen Gene Family." Elsevir,Amsterdam, 136 (1989)

[Publications] Nakazato,H.: "Gene and deduced primary structures of pregnancyーspecific beta1ーglycoproteins subfamily members within CEA family within immunoglobulin superfamily.In The Carcinoembryonic Antigen Gene Family." Elsevier,Amsterdam, 136 (1989)

松岡雄治福岡大学, 医学部, 教授 (70078773)