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

2011 Fiscal Year Final Research Report

• 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 (花村 典子) 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
• 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)
  • 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
  • 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] 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
  • 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
• [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
• [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
  • Total Pages: 414-422
  • Publisher: 文光堂
• [Remarks]
  • URL: http://www.medic.mie-u.ac.jp/organization/course/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: 特許、特願2010-170975
  • Filing Date: 2010-07-29