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June 2022 Mouse of the Month |
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がん研究注目の因子 Meflin(Islr)機能解析ツール
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| Meflin(Islr: Immunoglobulin Superfamily Containing Leucine Rich Repeat)は、GPI(glycosylphosphatidylinositol)型分泌膜タンパク質です。寄託者の榎本先生らによって、未分化な間葉系幹細胞、線維芽細胞の分子マーカーとして同定されました。がん研究分野においては、がん抑制性のがん関連線維芽細胞(CAF：cancer-associated fibroblast)の機能マーカーとして報告されています[1-4]。これまでに、Meflinは大腸がんや膵臓がん等各種がんにおいて、BMPシグナル経路等を介して、がん進行抑制に関与していることが明らかになっており、新規がん治療ターゲットとして注目を集めています[5-8]。すでにMeflinの発現を増強し、がん促進性CAFをがん抑制性CAFに変換させる化合物として合成レチノイドAM80が同定され、AM80と抗がん剤の併用の効果に関する治験も開始されています[9,10]。理研BRCからは、Meflinの機能解析、発現パターンの解析に有用なツールとして、Meflin KOマウス(RBRC09446)、Meflin タモキシフェン誘導型Creドライバーマウス(RBRC11436)、内在性Meflin プロモーター制御下で蛍光タンパク質ZsGreen、DTR(Diphtheria toxin receptor)、Cre酵素を同時に発現するレポーターマウス(RBRC11437)の3系統を提供可能です。Meflinが関わるがんのより詳細な分子メカニズムが明らかになることで、近い将来、臨床分野での実用化が実現することが期待されます。 |
| Depositor | : | 榎本 篤 先生 名古屋大学 |
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| Strain name | : | C57BL/6-Islr<tm1a(EUCOMM)Wtsi>/Ea | |
| RBRC No. | : | RBRC09446 | |
| Strain name | : | B6.129S6-Islr<tm1.1(cre/ERT2)Mat> | |
| RBRC No. | : | RBRC11436 | |
| Strain name | : | B6.129S6-Islr<tm1.1(ZsGreen/DTR/cre)Mat> | |
| RBRC No. | : | RBRC11437 | |
| References | : | [1] | Maeda K, Enomoto A, Hara A, Asai N, Kobayashi T, Horinouchi A, Maruyama S, Ishikawa Y, Nishiyama T, Kiyoi H, Kato T, Ando K, Weng L, Mii S, Asai M, Mizutani Y, Watanabe O, Hirooka Y, Goto H, Takahashi M. Identification of Meflin as a Potential Marker for Mesenchymal Stromal Cells. Sci Rep. 2016 Feb 29;6:22288. |
| [2] | Mizutani Y, Kobayashi H, Iida T, Asai N, Masamune A, Hara A, Esaki N, Ushida K, Mii S, Shiraki Y, Ando K, Weng L, Ishihara S, Ponik SM, Conklin MW, Haga H, Nagasaka A, Miyata T, Matsuyama M, Kobayashi T, Fujii T, Yamada S, Yamaguchi J, Wang T, Woods SL, Worthley D, Shimamura T, Fujishiro M, Hirooka Y, Enomoto A, Takahashi M. Meflin-Positive Cancer-Associated Fibroblasts Inhibit Pancreatic Carcinogenesis. Cancer Res. 2019 Oct 15;79(20):5367-5381. |
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| [3] | Miyai Y, Esaki N, Takahashi M, Enomoto A. Cancer-associated fibroblasts that restrain cancer progression: Hypotheses and perspectives. Cancer Sci. 2020 Apr;111(4):1047-1057. |
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| [4] | Kobayashi H, Gieniec KA, Wright JA, Wang T, Asai N, Mizutani Y, Lida T, Ando R, Suzuki N, Lannagan TRM, Ng JQ, Hara A, Shiraki Y, Mii S, Ichinose M, Vrbanac L, Lawrence MJ, Sammour T, Uehara K, Davies G, Lisowski L, Alexander IE, Hayakawa Y, Butler LM, Zannettino ACW, Din MO, Hasty J, Burt AD, Leedham SJ, Rustgi AK, Mukherjee S, Wang TC, Enomoto A, Takahashi M, Worthley DL, Woods SL. The Balance of Stromal BMP Signaling Mediated by GREM1 and ISLR Drives Colorectal Carcinogenesis. Gastroenterology.2021 Mar;160(4):1224-1239.e30. |
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| [5] | Miyai Y, Sugiyama D, Hase T, Asai N, Taki T, Nishida K, Fukui T, Chen-Yoshikawa TF, Kobayashi H, Mii S, Shiraki Y, Hasegawa Y, Nishikawa H, Ando Y, Takahashi M, Enomoto A. Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade. Life Sci Alliance. 2022 Mar 2;5(6):e202101230. |
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| [6] | Hara A, Kobayashi H, Asai N, Saito S, Higuchi T, Kato K, Okumura T, Bando YK, Takefuji M, Mizutani Y, Miyai Y, Saito S, Maruyama S, Maeda K, Ouchi N, Nagasaka A, Miyata T, Mii S, Kioka N, Worthley DL, Murohara T, Takahashi M, Enomoto A. Roles of the Mesenchymal Stromal/Stem Cell Marker Meflin in Cardiac Tissue Repair and the Development of Diastolic Dysfunction. Circ Res. 2019 Aug 2;125(4):414-430. |
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| [7] | Hara A, Kato K, Ishihara T, Kobayashi H, Asai N, Mii S, Shiraki Y, Miyai Y, Ando R, Mizutani Y, Iida T, Takefuji M, Murohara T, Takahashi M, Enomoto A. Meflin defines mesenchymal stem cells and/or their early progenitors with multilineage differentiation capacity. Genes Cells. 2021 Jul;26(7):495-512. |
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| [8] | Nakahara Y, Hashimoto N, Sakamoto K, Enomoto A, Adams TS, Yokoi T, Omote N, Poli S, Ando A, Wakahara K, Suzuki A, Inoue M, Hara A, Mizutani Y, Imaizumi K, Kawabe T, Rosas IO, Takahashi M, Kaminski N, Hasegawa Y. Fibroblasts positive for meflin have anti-fibrotic properties in pulmonary fibrosis. Eur Respir J. 2021 Dec 23;58(6):2003397. |
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| [9] | Mizutani Y, Iida T, Ohno E, Ishikawa T, Kinoshita F, Kuwatsuka Y, Imai M, Shimizu S, Tsuruta T, Enomoto A, Kawashima H, Fujishiro M. Safety and efficacy of MIKE-1 in patients with advanced pancreatic cancer: a study protocol for an open-label phase I/II investigator-initiated clinical trial based on a drug repositioning approach that reprograms the tumour stroma. BMC Cancer. 2022 Feb 24;22(1):205. |
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| [10] | Iida T, Mizutani Y, Esaki N, Ponik SM, Burkel BM, Weng L, Kuwata K, Masamune A, Ishihara S, Haga H, Kataoka K, Mii S, Shiraki Y, Ishikawa T, Ohno E, Kawashima H, Hirooka Y, Fujishiro M, Takahashi M, Enomoto A. Pharmacologic conversion of cancer-associated fibroblasts from a protumor phenotype to an antitumor phenotype improves the sensitivity of pancreatic cancer to chemotherapeutics. Oncogene. 2022 Apr 13. |
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| June 2022 Saori Mizuno, Ph.D. Contact: Experimental Animal Division, RIKEN BioResource Research Center (animal.brc@riken.jp) All materials contained on this site may not be reproduced, distributed, displayed, published or broadcast without the prior permission of the owner of that content. |
