Identification and clinical application of hedgehog signal inhibitors targeting feline mammary cancer stem cells

2013 Fiscal Year Final Research Report

• Project/Area Number: 24780314
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Clinical veterinary science
• Research Institution: Nippon Veterinary and Life Science University
• Principal Investigator: MICHISHITA Masaki 日本獣医生命科学大学, 獣医学部, 講師 (50434147)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 癌幹細胞 / 猫 / 乳腺腫瘍 / 分子標的薬

Research Abstract

Mammary carcinoma is the third most common cancer in cats. More than 80% of feline mammary tumors show considerable malignancy along with rapid progression and metastasis to the lung and local lymph node at an early stage. For cats with mammary carcinoma, effective chemotherapy is less established. A small population of cells known as tumor-initiating cells, which have the capacity to self-renew, differentiate, and form tumors at high frequency, has a potential role in tumor initiation, aggression, and recurrence. Therefore, novel therapeutic strategies are needed to improve the quality of life in felines with mammary gland tumors.
The present results demonstrated that hedgehog inhibitor GDC0449 inhibits sphere formation and ALDH activity, and had antitumor effects in a xenograft model of FKNp, suggesting that anti-tumor-initiating cells therapy with GDC0449 may be useful for treatment of feline mammary carcinoma.

Research Products

• [Journal Article] Identification of tumor-initiating cells in a canine hepatocellular carcinoma cell line (2014)
  • Author(s): Michishita M., Yasui J., Nakahira R., aya Y., Azakami D., Nakagawa T., Sasaki N., Arai T., Shida T, Takahashi K
  • Journal Title: Research in Veterinary Sciences Volume: 96 Pages: 315-322
  • Peer Reviewed
• [Journal Article] Investigation of the roles of fascioliasis and food allergy in intrahepatic eosinophilicproliferativepylephlebitis in Japanese Black cattle (2013)
  • Author(s): Kishida K, Ohkusu-Tsukada K., Hori M., Konnai M., Abiko C., Suzuki Y., Yamanome Y., Yoshimura H., Michishita M, Takahashi K
  • Journal Title: The veterinary Journal Volume: 196 Pages: 160-166
  • Peer Reviewed
• [Journal Article] Multiple inflammatory gastric polyps treated by endoscopic polypectomy with argon plasma coagulation in a dog (2013)
  • Author(s): Teshima T., Matsumoto H., Michishita M., Takahashi K., Koyama H
  • Journal Title: Journal of Small Animal Practice Volume: 54 Pages: 265-268
  • Peer Reviewed
• [Journal Article] Cell Cystadenoma of the Pancreas in a Cat (2013)
  • Author(s): Yoshimura H, Matsuda Y, Kawamoto Y, Michishita M, Ohkusu-Tsukada K, Takahashi K, Naito Z, Ishiwata T
  • Journal Title: Journal of Comparative Pathology Volume: 149 Pages: 225-228
  • Peer Reviewed
• [Journal Article] Antitumor Effect of Bevacizumab in a Xenograft Model of Canine Hemangiopericytoma (2013)
  • Author(s): Michishita M., Uto T., Nakazawa R., Yoshimura H., Ogihara K., Naya Y., Tajima T., Azakami D., Kishikawa S., Arai T., Takahashi K
  • Journal Title: Journal of Pharmacological Sciences Volume: 21 Pages: 339-342
• [Journal Article] Hepatocellular carcinoma in a young dog (2013)
  • Author(s): Teshima T., Matsumoto H., Shigihara H., Sawada H., Michishita M., Takahashi K., Koyama H
  • Journal Title: The Canadian Veterinary Journal Volume: 54 Pages: 845-848
  • Peer Reviewed
• [Journal Article] Mechanism of insulin production in canine bone marrow derived mesenchymal stem cells (2013)
  • Author(s): Takemitsu H., Yamamoto I., Zhao D., Michishita M., Arai T
  • Journal Title: General and Comparative Endocrinology Volume: 189 Pages: 1-6
  • Peer Reviewed
• [Journal Article] Molecular cloning and tumour suppressor function analysis of canine REIC/Dkk-3 in mammary gland tumours (2013)
  • Author(s): Ochiai K, Watanabe M, Azakami D., Michishita M, Yoshikawa Y., Udagawa C., Metheenukul P., Chahomchuen T., Aoki H., Kumon H., Morimitsum M., Omi T
  • Journal Title: The Veterinary Journal Volume: 197 Pages: 769-775
  • Peer Reviewed
• [Journal Article] Flow cytomeric analysis for detection of tumor-initiating cells in feline mammary carcinoma cell lines (2013)
  • Author(s): Michishita M., Otsuka A, Nakahira R, Nakagawa T., Sasaki N., Arai T., Takahashi K
  • Journal Title: Veterinary Immunology and Immunopathology Volume: 156 Pages: 73-81
  • Peer Reviewed
• [Journal Article] Apocrine sweat gland ductal adenoma with sebaceous differentiation in a dog (2013)
  • Author(s): Michishita M., Yasui J., Nakahira R., Yoshimura H., Takahashi K
  • Journal Title: Case Reports in Veterinary Medicine ID167923
  • DOI: 10.1155/2013/167923
  • Peer Reviewed
• [Journal Article] Amputation for histiocytic sarcoma in a cat (2012)
  • Author(s): Teshima T., Hata T., Nezu Y., Michishita M., Matsumoto H., Mizutani H., Takahashi K., Koyama H
  • Journal Title: Journal of Feline Medicine and Surgery Volume: 14 Pages: 147-150
  • Peer Reviewed
• [Journal Article] EP2 and EP4 receptors on muscularis resident macrophages mediate LPS-induced intestinal dysmotility via iNOS upregulation through cAMP/ERK signals (2012)
  • Author(s): Tajima T, Murata T, Aritake K, Urade Y, Michishita M, Matsuoka T, Narumiya S, Ozaki H, Hori M
  • Journal Title: American Journal of Physiology-Gastrointestinal and Liver Physiology Volume: 302 Pages: G524-G534
  • Peer Reviewed
• [Journal Article] Aldehyde dehydrogenase activity in cancer stem cells from canine mammary carcinoma cell lines (2012)
  • Author(s): Michishita M., Akiyoshi R., Suemizu H., Nakagawa T., Sasaki N., Takemitsu H, Arai T., Takahashi K
  • Journal Title: The Veterinary Journa Volume: 193 Pages: 508-513
  • Peer Reviewed
• [Journal Article] Comparison of bone marrow and adipose tissue-derived canine mesenchymal stem cells (2012)
  • Author(s): Takemitsu H., Zhao D., Yamamoto I., Harada Y., Michishita M., Arai T
  • Journal Title: BMC Veterinary Research Volume: 8 Pages: 150
  • Peer Reviewed
• [Presentation] フローサイトメトリー技術を用いた猫乳癌幹細胞の同定 (2013)
  • Author(s): 道下正貴、大塚綾、中川貴之、佐々木伸雄、新井敏郎、髙橋公正
  • Organizer: 第156回日本獣医学会学術集会
  • Place of Presentation: 岐阜
  • Year and Date: 20130920-22
• [Presentation] 乳腺腫瘍幹細胞研究 (2013)
  • Author(s): 道下正貴
  • Organizer: 予防動物医学研究会2013年度学術集会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2013-06-16
• [Presentation] 犬の肝癌幹細胞の同定と特徴づけ (2012)
  • Author(s): 道下正貴、江崎詩織、荻原喜久美、納谷裕子、呰上大吾、中川貴之、佐々木伸雄、新井敏郎、髙橋公正
  • Organizer: 第154回日本獣医学会学術集会
  • Place of Presentation: 岩手
  • Year and Date: 20120914-16
• [Presentation] 前立腺近傍に発生した犬の骨外性骨肉腫由来細胞株の性状解析 (2012)
  • Author(s): 小野沢栄里、呰上大吾、石岡克己、百田豊、左向敏紀、松田華奈、米野井瞳、宮部真裕、添田聡、道下正貴
  • Organizer: 第154回日本獣医学会学術集会
  • Place of Presentation: 岩手
  • Year and Date: 20120914-16
• [Remarks]
  • URL: https://ja-jp.facebook.com/nvluvetpathol