Title
Analysis of Primary and Metastatic Tumor in Fluorescent Protein
Expressing Metastasis Mouse Model : (1) Imaging
Nuclear-Cytoplasmic Dynamics in Primary and Metastatic Colon Cancer
in Nude Mice(2) Imaging the Role of Multinucleate Pancreatic
Cancer Cells and Cancer-Associated Fibroblasts in Peritoneal
Metastasis in Mouse Models( 要約版(Digest) )
Author(s)
長谷川, 恒輔
Report No.(Doctoral
Degree)
博士(医学) 甲第1067号
Issue Date
2018-03-25
Type
博士論文
Version
none
URL
http://hdl.handle.net/20.500.12099/75204
※この資料の著作権は、各資料の著者・学協会・出版社等に帰属します。࣏ࣜࢪࢺࣜ㛵ಀ㸦ู⣬㸲㸧
Repository㸦Form4㸧Ꮫㄽᩥせ⣙
Extended Summary in Lieu of the Full Text of a Doctoral Thesis
Ặ ྡ㸸
Full Name㛗㇂ᕝ ᜏ㍜
Ꮫㄽᩥ㢟┠㸸
Thesis Title$QDO\VLVRISULPDU\ DQG PHWDVWDWLFWXPRU LQIOXRUHVFHQW SURWHLQ H[SUHVVLQJPHWDVWDVLVPRXVHPRGHO ,PDJLQJ1XFOHDU&\WRSODVPLF'\QDPLFVLQ3ULPDU\DQGPHWDVWDWLF &RORQ&DQFHULQ1XGH0LFH ,PDJLQJWKH5ROHRI0XOWLQXFOHDWH3DQFUHDWLF&DQFHU&HOOV DQG &DQFHU$VVRFLDWHG)LEUREODVWVLQSHULWRQHDO0HWDVWDVLVLQ0RXVH 0RGHOV
Ꮫㄽᩥせ⣙㸸
Summary of Thesis ⮚ჾࡢ㌿⛣࣭ᾐ₶ࡣ⭠⒴࠾ࡼࡧ⮅⮚⒴ࢆࡣࡌࡵࡍࡿᵝࠎ࡞ᝏᛶ⭘⒆ࡢணᚋࢆつᐃࡍࡿࠋ㏆ᖺ⒴ ᚤᑠ⎔ቃ㸦70(7XPRUPLFURQHQYLURQPHQW㸧ࢆᵓᡂࡍࡿ⒴㛵㐃⥺⥔ⱆ⣽⬊㸦&DQFHU$VVRFLDWHG)LEUREODVW &$)㸧ࣜࣥࣃ⌫ᶞᯞ⣽⬊࣐ࢡࣟࣇ࣮ࢪ࡞ࡢ㛫㉁⣽⬊ࡀ⭘⒆ࡢ㌿⛣࣭ᾐ₶࠾࠸࡚㔜せ࡞ᙺࢆᯝࡓࡋ ࡚࠸ࡿࡇࡀሗ࿌ࡉࢀ࡚࠸ࡿࠋᚑࡗ࡚ཎⓎᕢࡸ㌿⛣ᕢ࠾ࡅࡿ⒴⣽⬊࠾ࡼࡧ⒴࿘ᅖ⣽⬊ࡢᙧែኚ࣭ືែゎ ᯒ㛵ࡍࡿ◊✲ࡣᝏᛶᝈࡢணᚋᨵၿࢆࡵࡊࡍୖ࡛ᴟࡵ࡚㔜せ࡛࠶ࡿࠋᮏ◊✲࡛ࡣ㸪㸦㸧⥳Ⰽ⺯ගࢱࣥࣃࢡ ㉁㸦*UHHQIOXRUHVFHQW3URWHLQ*)3㸧ࢆ᰾ෆࣄࢫࢺࣥ +% ࡲࡓ㉥Ⰽ⺯ගࢱࣥࣃࢡ㉁㸦5HG)OXRUHVFHQW 3URWHLQ5)3㸧ࢆ⣽⬊㉁ࡑࢀࡒࢀᑟධࡋࡓ⭠⒴ᰴࢾ࣮ࢻ࣐࢘ࢫࢆ⏝࠸࡚⭠⒴㌿⛣ࣔࢹࣝࢆసᡂࡋ ཎⓎᕢ㌿⛣ᕢࡢ⒴⣽⬊࿘ᮇ㸦ᙧែ࣭ศീ㸧ࡢ┦㐪ࢆゎᯒࡍࡿࡇࡲࡓ㸦㸧*)3 ࢆᑟධࡉࢀࡓ⮅⮚⒴ᰴ ࢾ࣮ࢻ࣐࢘ࢫࢆ⏝࠸࡚⮅⮚⒴㌿⛣ࣔࢹࣝࢆసᡂࡋ⒴࠾ࡼࡧ 70( ᵓᡂ⣽⬊ࡢᙧែ⭘⒆ቑṪ⬟ࢆゎᯒࡍࡿ ࡇ࡛⒴ཎⓎᕢ㌿⛣ᕢ࠾ࡅࡿ⒴⣽⬊⭘⒆㛫㉁⣽⬊ࡢ⣽⬊ືែ࠾ࡼࡧ┦స⏝ࡘ࠸᳨࡚ウࡋࡓࠋ ࠙ᑐ㇟᪉ἲࠚ 㸦㸧⭠⒴ᰴࡣ UHWURYLUXVYHFWRU ࢆ⏝࠸࡚ *)3࣭5)3 ࢆᑟධࡉࢀࡓࠊࣄࢺ⏤᮶ࡢ⤖⭠⭢⒴ᰴ㸦+&7*)35)3㸧 ࢆ⏝࠸ࡓࠋ 㐌㱋ࡢ %$/%FQXQX ࣐࢘ࢫ +&7*)35)3 ⣽⬊ࢆ ಶ⭁ὀࡋ⭠⒴㌿⛣ࣔࢹࣝࢆసᡂ ࡋࡓࠋ ᪥ᚋ࣐࢘ࢫࢆゎ๗ࡋཎⓎᕢ㌿⛣ᕢࡢH[YLYR࣓࣮ࢪࣥࢢࢆ⾜࠸ࡉࡽ⭘⒆ሢෆ⣽⬊ࢆᇵ㣴 ࡋ࡚ほᐹࡋࡓࠋ㸦㸧⮅⮚⒴ᰴࡣ UHWURYLUXVYHFWRU ࢆ⏝࠸࡚ *)3 ࢆᑟධࡉࢀࡓࣄࢺ⏤᮶ࡢ⮅⮚⭢⒴ᰴ㸦%[3& 㸱Ѹ*)3㸧ࢆ⏝࠸ࡓࠋ 㐌㱋ࡢ %$/%FQXQX ࣐࢘ࢫ %[3&*)3 ࢆ ಶ⓶ୗὀࡋ⓶ୗ⭘⒆ࢆసᡂࡋࡓࠋ ᪥ᚋྠ⭘⒆ࢆฟࡋ⭘⒆ሢෆ⣽⬊ࢆᇵ㣴࣭ほᐹࡍࡿࡶฟࡋࡓ⓶ୗ⭘⒆ࢆ PPࡢ⭘⒆∦ศ ࡋ࡚ 㐌㱋ࡢ %$/%FQXQX ࣐࢘ࢫࡢ⮅ᑿ㒊⛣᳜ࡋ⮅⮚⒴㌿⛣ࣔࢹࣝࢆసᡂࡋࡓࠋ 㐌ᚋ࣐࢘ࢫࢆ㛤⭡ ࡋཎⓎᕢ㌿⛣ᕢࡢゎᯒ㸦ཎⓎᕢ࠾ࡼࡧ㌿⛣ᕢࡢ࣓࣮ࢪࣥࢢྛ⭘⒆ሢෆ⣽⬊ࡢᇵ㣴ほᐹ㸧ࢆ⾜ࡗࡓࠋࡲ ࡓཎⓎᕢ࠾ࡼࡧ㌿⛣ᕢࡼࡾ᥇ྲྀࡋࡓ⭘⒆ሢෆ⣽⬊ࢆᇵ㣴ࡋ 㐌㱋ࡢ %$/%FQXQX ࣐࢘ࢫࡢ⫼㒊ࡑࢀࡒࢀ ಶ⓶ୗὀࡋ⓶ୗ⭘⒆ࢆసᡂࡋࡓࠋ ᪥ᚋ⭘⒆ࢆฟࡋ⭘⒆ᚄ㔜㔞ࢆホ౯ࡍࡿࡶ⭘⒆ෆ⣽ ⬊ࢆᗘᇵ㣴㸦 㐌㛫㸧ࡋ࡚ᙧែኚࢆホ౯ࡋࡓࠋ⺯ගᑟධ⣽⬊ࡢほᐹࡣ 6=;PLFURVFRSH)9FRQIRFDO PLFURVFRSH㸦2O\PSXV㸧'LQROLWHGLJLWDOIOXRUHVFHQFHPLFURVFRS\ ࢆ⏝࠸ࡓࠋ ࠙⤖ᯝࠚ 㸦㸧+&7*)35)3 ⣽⬊ࢆ⭁ὀࡋࡓ ᪥ᚋ%$/%FQXQX ࣐࢘ࢫࡢ⫢⮚࠾ࡼࡧᚋ⭡⭷㌿⛣ࢆㄆࡵࡓࠋ *)35)3 ඹⓎ⌧⣽⬊ࡣ⫢㌿⛣ᕢ࡛ࡶࡗࡶከࡃㄆࡵࡓࠋཎⓎᕢ㸦⭁⮚㸧࠾ࡼࡧྛ㌿⛣ᕢ㸦⫢⮚࠾ࡼࡧᚋ⭡⭷㸧 ࡢ⤌⧊ᇵ㣴࡛ࡣ⣽⬊ศീࡸከᩘࡢ✵◙ࢆᣢࡘᕧ࡞ከ᰾⒴⣽⬊ࢆㄆࡵࡓ⫢㌿⛣ᕢ࡛ࡢࡳ⣳㗽≧ࡢ⒴ ⣽⬊ࢆㄆࡵࡓࠋከ᰾⒴⣽⬊⣽⬊ศീࡢẚ⋡ࢆཎⓎᕢྛ㌿⛣ᕢࡢ⤌⧊ᇵ㣴࡚☜ㄆࡋࡓࡇࢁྛ⤌⧊ 㛫࡛᭷ព࡞ᕪ␗ࡣㄆࡵࡽࢀ࡞ࡗࡓࠋ㸦㸧%[3&*)3 ⣽⬊⓶ୗ⭘⒆ࢆ⮅ᑿ㒊⛣᳜ࡋࡓ 㐌ᚋ⛣᳜㒊㸦ཎⓎᕢ㸧ࡢ⭘⒆ᙧᡂ⭡⭷✀ࢆㄆࡵࡓࠋཎⓎᕢ࠾ࡼࡧ⭡⭷✀ᕢࡢ⤌⧊ᇵ㣴࡛ࡣ⭡⭷✀ᕢ࡛᭷ពከᩘࡢ ከ᰾⒴⣽⬊ࡢฟ⌧ࢆㄆࡵࡓ㸦S 㸧ࠋཎⓎᕢ࠾ࡼࡧ⭡⭷✀ᕢࡢᇵ㣴⣽⬊ࢆࡑࢀࡒࢀ %$/%FQXQX ࣐࢘ ࢫ⓶ୗὀࡋ ᪥ᚋᙧᡂࡉࢀࡓ⓶ୗ⭘⒆ࢆホ౯ࡋࡓࡇࢁ⭡⭷✀ᕢ⏤᮶ࡢ⓶ୗ⭘⒆ࡣཎⓎᕢ⏤᮶ࡢ ⭘⒆ẚ㍑ࡋ࡚᭷ព⭘⒆㔜㔞ࡀቑຍࡋ࡚࠸ࡓ㸦S 㸧ࠋࡲࡓฟࡋࡓ⓶ୗ⭘⒆ࢆࡑࢀࡒࢀ⤌⧊ᇵ㣴ࡋ࡚ ほᐹࡋࡓࡇࢁ⭡⭷✀ᕢ⏤᮶ࡢ⓶ୗ⭘⒆⤌⧊࡛ࡣཎⓎᕢ⏤᮶ࡢ⤌⧊ẚ㍑ࡋ࡚ከᩘࡢ⥺⥔ⱆ⣽⬊ከ᰾ ⒴⣽⬊ࢆㄆࡵࡓࠋ ࠙⪃ᐹࠚ ⭠⒴࠾ࡼࡧ⮅⮚⒴⣽⬊ࢆ⏝࠸࡚㌿⛣ࣔࢹࣝࢆసᡂࡋཎⓎᕢ㌿⛣ᕢࢆᵓᡂࡍࡿ⣽⬊ࡢ✀㢮࠾ࡼࡧᙧែ ࢆゎᯒࡋࡓࠋ⭠⒴࠾ࡼࡧ⮅⮚⒴ࡶཎⓎᕢࡢ㏻ᖖ⥅௦ࡼࡿ⤌⧊ᇵ㣴࡛ࡣㄆࡵࡽࢀ࡞ࡗࡓከ᰾⒴⣽⬊ ࡀ㌿⛣ᕢࡢ⤌⧊ᇵ㣴࠾࠸࡚ከᩘฟ⌧ࡋ࡚࠸ࡓࠋࡲࡓ⮅⮚⒴ࡢ㌿⛣ᕢ࠾࠸࡚ࡣ࣐࢘ࢫ⏤᮶ࡢ⒴㛵㐃⥺⥔ ⱆ⣽⬊ࢆከᩘㄆࡵࡓࡇࡼࡾᮏ◊✲࡛☜ㄆࡉࢀࡓከ᰾⒴⣽⬊ࡸ⥺⥔ⱆ⣽⬊ࡀ⒴ࡢ㌿⛣ࡉࡽࡣ㌿⛣ᕢ࠾ ࡅࡿ⭘⒆⣽⬊ࡢቑṪ㛵ࡋ࡚࠸ࡿྍ⬟ᛶࡀ♧၀ࡉࢀࡓࠋ ࠙⤖ㄽࠚ ᅇసᡂࡋࡓ⭠⒴࠾ࡼࡧ⮅⮚⒴㌿⛣ື≀ࣔࢹࣝࡣཎⓎᕢ࠾ࡼࡧ㌿⛣ᕢ࠾ࡅࡿ⒴⣽⬊⭘⒆㛫㉁⣽⬊ ࡢᙧែ࠾ࡼࡧືែࢆゎᯒࡍࡿୖ࡛᭷⏝࡞ᐇ㦂⣔࡛࠶ࡿࠋᮏ◊✲࡛♧ࡉࢀࡓከ᰾⒴⣽⬊ࡸ⭘⒆㛫㉁࠾ࡅࡿ⥺ ⥔ⱆ⣽⬊ࡣ⭘⒆⣽⬊ࡢቑṪ࣭㌿⛣῝ࡃ㛵ࡋ࡚࠾ࡾ⒴ࡢᾐ₶࣭㌿⛣ࢆไᚚࡍࡿୖ࡛㔜せ࡞ᶆⓗ࡞ࡿྍ ⬟ᛶࡀ࠶ࡿࠋ