Incomplete epithelial-mesenchymal transition of breast cancer cells during cancer progression and its regulatory mechanism

• Project/Area Number: 21590368
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Mie University
• Principal Investigator: YOSHIDA Toshimichi 三重大学, 大学院・医学系研究科, 教授 (80166959)
• Co-Investigator(Kenkyū-buntansha): HANAMURA Noriko 三重大学, 医学部附属病院, 講師 (60437100) ; SHIMOJO Naoshi 三重大学, 医学部, 技術員 (70410751)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: テネイシン-C / 上皮間葉移行 / 乳癌

Research Abstract

High expression of tenascin-C(TNC) has been demonstrated in invasive fronts of various cancers including breast cancer. We found the more extensive expression in invading areas of the small cancer nests. TNC treatment in vitro induced epithelia mesenchymal transition(EMT)-like change of breast cancer cells MCF7, that was enhanced by additional transforming growth factor-beta1. We also showed the contribution of alphαvbeta6 and alphαvbeta1 integrins to this phenotypic change. Activation of FAK and SRC forming integrin adhesion complex was associated with EMT change. Immunohistochemistry of the integrins showed their expression in human breast cancer tissues.

Research Products

• [Journal Article] Imatinib mesylate prevents cerebral vasospasm after subarachnoid hemorrhage via inhibiting tenascin-C expression in rats (2012)
  • Author(s): Shiba M, Suzuki H, Fujimoto M, Shimojo N, Imanaka-Yoshida K, Yoshida T, Kanamaru K, Matsushima S, Taki W
  • Journal Title: Neurobiol Dis Volume: 46(1) Pages: 172-9
  • Peer Reviewed
• [Journal Article] Role of stromal myofibroblasts in invasive breast cancer : stromal expression of alpha-smooth muscle actin correlates with worse clinical outcome (2011)
  • Author(s): Yamashita M, Ogawa T, Zhang X, Hanamura N, Kashikura Y, Takamura M, Yoneda M, Shiraishi T
  • Journal Title: Breast Cancer Volume: (in press)
  • NAID: 10030981091
  • Peer Reviewed
• [Journal Article] Toward in vivo imaging of heart disease using a radiolabeled single-chain Fv fragment targeting tenascin-C (2011)
  • Author(s): Kobayashi N, Odaka K, Uehara T, Imanaka-Yoshida K, Kato Y, Oyama H, Tadokoro H, Akizawa H, Tanada S, Hiroe M, Fukumura T, Komuro I, Arano Y, Yoshida T, Irie T
  • Journal Title: Anal Chem Volume: 83(23) Pages: 9123-30
  • Peer Reviewed
• [Journal Article] α9β1 integrin-mediated signaling serves as an intrinsic regulator of pathogenic Th17 cell generation (2011)
  • Author(s): Kanayama M, Morimoto J, Matsui Y, Ikesue M, Danzaki K, Kurotaki D, Ito K, Yoshida T, Uede T
  • Journal Title: J Immunol Volume: 187(11) Pages: 5851-64
  • Peer Reviewed
• [Journal Article] Tenascin-C is expressed in abdominal aortic aneurysm tissue with an active degradation process (2011)
  • Author(s): Kimura T, Yoshimura K, Aoki H, Imanaka-Yoshida K, Yoshida T, Ikeda Y, Morikage N, Endo H, Hamano K, Imaizumi T, Hiroe M, Aonuma K, Matsuzaki M
  • Journal Title: Pathol Int Volume: 61(10) Pages: 559-64
  • NAID: 10030721173
  • Peer Reviewed
• [Journal Article] enascin-C enhances crosstalk signaling of integrinαvβ3/PDGFR-βcomplex by SRC recruitment promoting PDGF-induced proliferation and migration in smooth muscle cells (2011)
  • Author(s): Ishigaki T, Imanaka-Yoshida K, Shimojo N, Matsushima S, Taki W, Yoshida T
  • Journal Title: J Cell Physiol Volume: 226(10) Pages: 2617-24
  • Peer Reviewed
• [Journal Article] Tenascin C may regulate the recruitment of smooth muscle cells during coronary artery development (2011)
  • Author(s): Ando K, Takahashi M, Yamagishi T, Miyagawa-Tomita S, Imanaka-Yoshida K, Yoshida T, Nakajima Y
  • Journal Title: Differentiation Volume: 81(5) Pages: 299-306
  • Peer Reviewed
• [Journal Article] Cerebrospinal fluid tenascin-C in cerebral vasospasm after aneurysmal subarachnoid hemorrhage (2011)
  • Author(s): Suzuki H, Kanamaru K, Shiba M, Fujimoto M, Imanaka-Yoshida K, Yoshida T, Taki W
  • Journal Title: J Neurosurg Anesthesiol Volume: 23(4) Pages: 310-7
  • Peer Reviewed
• [Journal Article] Tenascin C induces epithelial-mesenchymal transition-like change accompanied by SRC activation and focal adhesion kinase phosphorylation in human breast cancer cells (2011)
  • Author(s): Nagaharu K, Zhang X, Yoshida T, Katoh D, Hanamura N, Kozuka Y, Ogawa T, Shiraishi T, Imanaka-Yoshida K
  • Journal Title: Am J Pathol Volume: 178(2) Pages: 754-63
  • Peer Reviewed
• [Journal Article] Toward in vivo imaging of heart disease using a radiolabeled single-chain Fv fragment targeting tenascin-C (2011)
  • Author(s): Kobayashi N, Odaka K, Uehara T, Imanaka-Yoshida K, Kato Y, Oyama H, Tadokoro H, Akizawa H, Tanada S, Hiroe M, Fukumura T, Komuro I, Arano Y, Yoshida T, Irie T
  • Journal Title: ANALYTICAL CHEMISTRY Volume: 83 Issue: 23 Pages: 9123-9130
  • DOI: 10.1021/ac202159p
  • Peer Reviewed
• [Journal Article] Tenascin-C Enhances Crosstalk Signaling of Integrin alpha v beta 3/PDGFR-beta Complex by SRC Recruitment Promoting PDGF-Induced Proliferation and Migration in Smooth Muscle Cells (2011)
  • Author(s): Ishigaki T, Imanaka-Yoshida K, Shimojo N, Matsushima S, Taki W, Yoshida T
  • Journal Title: JOURNAL OF CELLULAR PHYSIOLOGY Volume: 226 Issue: 10 Pages: 2617-2624
  • DOI: 10.1002/jcp.22614
  • Peer Reviewed
• [Journal Article] Alpha9beta1 integrin-mediated signaling servesas an intrinsic regulator of pathog- enic Th17 cell generation (2011)
  • Author(s): Kanayama M, Morimoto J, Matsui Y, I- kesue M, Danzaki K, Kurotaki D, Ito K, Yoshida T, Uede T
  • Journal Title: J Immunol Volume: 187 Issue: 11 Pages: 5851-64
  • DOI: 10.4049/jimmunol.1101524
  • Peer Reviewed
• [Journal Article] Role of stromal myofibroblasts in invasive breast cancer : stromal expression of alpha-smooth muscle actin correlates with worse clinical outcome. (2011)
  • Author(s): Yamashita M, Ogawa T, Zhang X, Hanamura N, Kashikura Y, Takamura M, Yoneda M, Shiraishi T.
  • Journal Title: Breast Cancer. Volume: (in press)
  • NAID: 10030981091
  • Peer Reviewed
• [Journal Article] Tenascin C induces epithelial-mesenchymal transition-like change accompanied by SRC activation and focal adhesion kinase phosphorylation in human breast cancer cells. (2011)
  • Author(s): Nagaharu K, Zhang X, Yoshida T, Katoh D, Hanamura N, Kozuka Y, Ogawa T, Shiraishi T, Imanaka-Yoshida K.
  • Journal Title: Am J Pathol. Volume: 178 Pages: 754-763
  • Peer Reviewed
• [Journal Article] Tenascin-C enhances crosstalk signaling of integrin αvβ3/PDGFR-β complex by SRC recruitment promoting PDGF-induced proliferation and migration in smooth muscle cells. (2011)
  • Author(s): Ishigaki T, Imanaka-Yoshida K, Shimojo N, Matsushima S, Taki W, Yoshida T.
  • Journal Title: J Cell Physiol. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Dynamic expression of tenascin-C after myocardial ischemia and reperfusion : assessment by 125I-anti-tenascin-C antibody imaging (2010)
  • Author(s): Taki J, Inaki A, Wakabayashi H, Imanaka-Yoshida K, Ogawa K, Hiroe M, Shiba K, Yoshida T, Kinuya S
  • Journal Title: J Nucl Med Volume: 51(7) Pages: 1116-22
  • Peer Reviewed
• [Journal Article] Deficiency of tenascin-C delays articular cartilage repair in mice (2010)
  • Author(s): Okamura N, Hasegawa M, Nakoshi Y, Iino T, Sudo A, Imanaka-Yoshida K, Yoshida T, Uchida A
  • Journal Title: Osteoarthritis Cartilage Volume: 18(6) Pages: 839-48
  • Peer Reviewed
• [Journal Article] Distribution and role of tenascin-C in human osteoarthritic cartilage (2010)
  • Author(s): Nakoshi Y, Hasegawa M, Akeda K, Iino T, Sudo A, Yoshida T, Uchida A
  • Journal Title: J Orthop Sci Volume: 15(5) Pages: 666-73
  • NAID: 10027872151
  • Peer Reviewed
• [Journal Article] Tenascin-C may aggrαvate left ventricular remodeling and function after myocardial infarction in mice (2010)
  • Author(s): Nishioka T, Onishi K, Shimojo N, Nagano Y, Matsusaka H, Ikeuchi M, Ide T, Tsutsui H, Hiroe M, Yoshida T, Imanaka-Yoshida K
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 298(3) Pages: 1072-8
  • Peer Reviewed
• [Journal Article] Tenascin-C is induced in cerebral vasospasm after subarachnoid hemorrhage in rats and humans : a pilot study (2010)
  • Author(s): Suzuki H, Kanamaru K, Suzuki Y, Aimi Y, Matsubara N, Araki T, Takayasu M, Kinoshita N, Imanaka-Yoshida K, Yoshida T, Taki W
  • Journal Title: Neurol Res Volume: 32(2) Pages: 179-84
  • Peer Reviewed
• [Journal Article] Incremental prognostic values of serum tenascin-C levels with blood B-type natriuretic peptide testing at discharge in patients with dilated cardiomyopathy and decompensated heart failure (2009)
  • Author(s): Fujimoto N, Onishi K, Sato A, Terasaki F, Tsukada B, Nozato T, Yamada T, Imanaka-Yoshida K, Yoshida T, Ito M, Hiroe M
  • Journal Title: J Card Fail Volume: 15(10) Pages: 898-905
  • Peer Reviewed
• [Journal Article] High prevalence of chronic myocarditis in dilated cardiomyopathy referred for left ventriculoplasty : expression of tenascin C as a possible marker for inflammation (2009)
  • Author(s): Tsukada B, Terasaki F, Shimomura H, Otsuka K, Otsuka K, Katashima T, Fujita S, Imanaka-Yoshida K, Yoshida T, Hiroe M, Kitaura Y
  • Journal Title: Hum Pathol Volume: 40(7) Pages: 1015-22
  • Peer Reviewed
• [Journal Article] 乳腺紡錘細胞癌の1例 (2009)
  • Author(s): 花村典子, 小川朋子, 山下雅子, 三井貴子, 柏倉由実, 張心慧, 小塚祐司, 白石泰三
  • Journal Title: 乳癌の臨床 24 Pages: 537-540
  • Peer Reviewed
• [Presentation] テネイシン-CはインテグリンαVβ6、α2β1を介して乳癌細胞の上皮間葉移行を誘導する (2011)
  • Author(s): 吉田利通
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市・国際会議場
  • Year and Date: 2011-10-05
• [Presentation] テネイシン-Cはインテグリンとシンデカン-4を介して乳癌細胞の上皮間葉移行を誘導する (2011)
  • Author(s): 加藤大祐、下條尚志、今中恭子、吉田利通
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜市・パシフィコ横浜
  • Year and Date: 2011-04-30
• [Presentation] 創傷治癒関連因子と乳癌の予後との検討 (2010)
  • Author(s): 山下雅子、小川朋子、柏倉由実、木村弘子、花村典子、白石泰三
  • Organizer: 日本乳癌学会
  • Place of Presentation: ロイトン札幌、札幌
• [Presentation] 浸潤性乳癌においてα-SMAは予後因子になりうるか (2010)
  • Author(s): 山下雅子、小川朋子、張心慧、柏倉由実、三井弘子、花村典子、白石泰三
  • Organizer: 日本外科学会
  • Place of Presentation: 名古屋国際会議場、名古屋
• [Presentation] 当院での乳腺穿針吸引細胞診の精度と乳癌術前診断方法 (2010)
  • Author(s): 花村典子、小川朋子、山下雅子、木村弘子、柏倉由実、今井裕、白石泰三
  • Organizer: 日本乳癌学会
  • Place of Presentation: ロイトン札幌・札幌
• [Presentation] テナイシン-Cは乳癌細胞の上皮間葉移行を誘導する (2009)
  • Author(s): 吉田利通, 永春圭規, 小塚祐司, ほか
  • Organizer: オステポンチン研究会
  • Place of Presentation: 北海道大学
  • Year and Date: 2009-09-13
• [Presentation] 粗大石灰化を伴う線維腺腫に合併した乳癌の2例 (2009)
  • Author(s): 花村典子, 山下雅子, 小川朋子, 柏倉由実, 三井貴子, 張心慧, 今井裕, 白石泰三
  • Organizer: 第6回日本乳癌学会中部地方会
  • Place of Presentation: アクトシティー浜松
  • Year and Date: 2009-09-12
• [Presentation] テネイシン-Cは乳癌細胞の上皮間葉移行を誘導する (2009)
  • Author(s): 永春圭規, 吉田利通, 今中恭子
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 国立京都国際会館
• [Presentation] テネイシン-Cは乳癌細胞の上皮間葉移行を誘導する (2009)
  • Author(s): 吉田利通
  • Organizer: 第19回乳癌基礎研究会
  • Place of Presentation: 伊香保温泉森秋旅館
• [Presentation] テナイシン-Cは乳癌細胞の不完全型上皮間葉移行を誘導する (2009)
  • Author(s): 吉田利通
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
• [Book] 病理診断に役立つ分子生物学 (2011)
  • Author(s): 吉田利通、今中恭子
  • Publisher: 文光堂
• [Book] 病理診断に役立つ分子生物学(病理と臨床臨時増刊号) (2011)
  • Author(s): 吉田利通、今中恭子
  • Publisher: 文光堂
• [Remarks]
  • URL: http://www.medic.mie-u.ac.jp/organization/course/pathol_matrix/
• [Remarks]
  • URL: http://www.medic.mie-u.ac.jp/pathol_matrix/
• [Patent(Industrial Property Rights)] 抗腫瘍剤 (2010)
  • Inventor(s): 深井文雄、吉田利通
  • Industrial Property Rights Holder: 東京理科大、三重大
  • Industrial Property Number: 2010-170975
  • Filing Date: 2010-07-29