Lymphangiogenesis in cancer

2009 Fiscal Year Final Research Report

• Project/Area Number: 17014047
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University
• Principal Investigator: KUBO Hajime Kyoto University, 医学研究科, 講師 (50362520)
• Project Period (FY): 2005 – 2009
• Keywords: リンパ管新生 / 転移 / がん幹細胞

Research Abstract

To find the way of the inhibition of metastasis is important for cancer therapy. We found 2 important mechanisms in metastasis; 1) the role of lymphagiogenesis, 2) the induction of cancer stem cells from non-cancer stem cells. Lymphangiogenesis promotes the metastasis. We succeeded the inhibition of metastasis by anti-lymphangiogenesis therapy in mouse model. However, we found that cancer stem cells don't have the potential of lymphangiogenesis. To inhibit the metastasis, it could be important to target the induction of cancer stem cells in the metastatic sites.

Research Products

• [Journal Article] Hepatic Stellate Cells Promote Liver Metastasis of Colon Cancer Cells by the Action of SDF-1/CXCR4 Axis. (2009)
  • Author(s): Matsusue R, * Kubo H, Hisamori S, Okoshi K, Takagi H, Hida K, Nakano K, Itami A, Kawada K, Nagayama S, Sakai Y.
  • Journal Title: Ann Surg Oncol. 16(9) Pages: 2645-53
  • Peer Reviewed
• [Journal Article] Inverse correlation of the up-regulation of FZD10 expression and the activation of beta-catenin in synchronous colorectal tumors. (2008)
  • Author(s): Nagayama S, Yamada E, Kohno Y, Aoyama T, Fukukawa C, Kubo H, Watanabe G, Katagiri T, Nakamura Y, Sakai Y, Toguchida J.
  • Journal Title: Cancer Sci. 2009 Mar 100(3) Pages: 405-12
  • Peer Reviewed
• [Journal Article] All-trans-retinoic acid attenuates radiation-induced intestinal fibrosis in mice. (2008)
  • Author(s): Kae Okoshi, * Hajime Kubo, Satoshi Nagayama, Chiharu Tabata, Yoshio Kadokawa, Shigeo Hisamori, Yoshikuni Yonenaga, Akihisa Fujimoto, Akira Mori, Hisashi Onodera, Go Watanabe, Yoshiharu Sakai
  • Journal Title: J Surg Res. 150 Pages: 53-59
  • Peer Reviewed
• [Journal Article] All-trans-retinoic acid ameliorates carbon tetrachloride-induced liver fibrosis in mice through modulating cytokine production. (2008)
  • Author(s): Shigeo Hisamori, Chiharu Tabata, Yoshio Kadokawa, Kae Okoshi, Rie Tabata, Akira Mori, Satoshi Nagayama, Go Watanabe, * Hajime Kubo, Yoshiharu Sakai
  • Journal Title: Liver Int. 28 Pages: 1217-1225
  • Peer Reviewed
• [Journal Article] Immunohistochemical detection of the lymphatic marker podoplanin in diverse types of human cancer cells using a novel antibody. (2007)
  • Author(s): Kono T, Shimoda M, Takahashi M, Matsumoto K, Yoshimoto T, Mizutani M, Tabata C, Okoshi K, Wada H, *Kubo H
  • Journal Title: Int J Oncol. 31(3) Pages: 501-8
  • Peer Reviewed
• [Journal Article] RNA mutations of prox1 detected in human esophageal cancer cells by the shifted termination assay. (2007)
  • Author(s): Yoshimoto T, Takahashi M, Nagayama S, Watanabe G, Shimada Y, Sakai Y, * Kubo H
  • Journal Title: BBRC 359(2) Pages: 258-62
  • Peer Reviewed
• [Journal Article] The Perivascular space as a path of Hematopoietic progenitor cells and Mature T cells between the blood circulation and the Thymic parenchyma. (2007)
  • Author(s): Mori M, Itoi M, Taukamoto N, Kubo H, Amagai T
  • Journal Title: Int Immunol. 19(6) Pages: 745-53
  • Peer Reviewed
• [Journal Article] Thalidomide prevents bleomycin-induced pulmonary fibrosis in mice. (2007)
  • Author(s): Tabata C, Tabata R, Kadokawa Y, Hisamori S, Takahashi M, Mishima M, Nakano T, Kubo H
  • Journal Title: J Immunol. 179(1) Pages: 708-14
  • Peer Reviewed
• [Journal Article] Prox1 Induces Lymphatic Endothelial Differentiation via Integrin {alpha}9 and Other Signaling Cascades. (2007)
  • Author(s): Mishima K, Watabe T, Saito A, Yoshimatsu Y, Imaizumi N, Masui S, Hirashima M, Morisada T, Oike Y, Araie M, Niwa H, Kubo H, Suda T, Miyazono K
  • Journal Title: Mol Biol Cell. 18(4) Pages: 1421-9
  • Peer Reviewed
• [Journal Article] Two populations of Thy1-positive mesenchymal cells regulate the in vitro maturation of hepatic progenitor cells. (2007)
  • Author(s): Kamo N, Yasuchika K, Fujii H, Hoppo T, Machimoto T, Ishii T, Fujita N, Tsuruo T, Yamashita JK, *Kubo H, Ikai I
  • Journal Title: Am J Physiol Gastr Liver Physiol. 292 Pages: G526-534
  • Peer Reviewed
• [Journal Article] Loss of function of the candidate tumor suppressor prox1 by RNA mutation in human cancer cells. (2006)
  • Author(s): Takahashi M, Yoshimoto T, Shimoda M, Kono T, Koizumi M, Yazumi S, Shimada Y, Doi R, Chiba T, *Kubo H
  • Journal Title: Neoplasia 8 Pages: 1003-1010
  • Peer Reviewed
• [Journal Article] All-trans-retinoic acid prevents radiation- or bleomycin-induced pulmonary fibrosis. (2006)
  • Author(s): Tabata C, Kadokawa Y, Tabata R, Takahashi M, Okoshi K, Sakai Y, Mishima M, Kubo H
  • Journal Title: Am J Respir Crit Care Med. 174 Pages: 1352-60
  • Peer Reviewed
• [Journal Article] A homeobox protein prox1 is involved in the differentiation, proliferation and prognosis in hepatocellular carcinoma. (2006)
  • Author(s): Shimoda M, Takahashi M, Yoshimoto T, Kono T, Ikai I, *Kubo H
  • Journal Title: Clin Cancer Res. 12 Pages: 6005-11
  • Peer Reviewed
• [Journal Article] All-trans retinoic acid modulates proliferation of lung fibroblasts via IL-6/IL-6R system. (2006)
  • Author(s): Tabata C, Kubo H, Tabata R, Wada M, Sakuma K, Ichikawa M, Fujita S, Mio T, Mishima M
  • Journal Title: Am J Physiol Lung Cell Mol Physiol. 290 Pages: L597-L606
  • Peer Reviewed
• [Journal Article] Differentiation of lymphatic endothelial cells from Embryonic Stem cells on OP9 stromal cells. (2006)
  • Author(s): Kono T, *Kubo H (equally first author), Shimazu C, Ueda Y, Takahashi M, Yanagi K, Fujita N, Tsuruo T, Wada H, Yamashita JK
  • Journal Title: Arterioscler Thromb Vasc Biol. 26 Pages: 2070-2076
  • Peer Reviewed
• [Journal Article] Vascular endothelial growth factor-D is dispensable for development of the lymphatic system. (2005)
  • Author(s): Baldwin ME, Halford MM, Roufail S, Williams RA, Hibbs ML, Grail D, Kubo H, Stacker SA, Achen MG
  • Journal Title: Mol Cell Biol. 25 Pages: 2441-9
  • Peer Reviewed
• [Journal Article] Lymphangiogenesis-Mediated Shedding of LAM Cell Clusters as a Mechanism for Dissemination in Lymphangioleiomyomatosis. (2005)
  • Author(s): Kumasaka T, Seyama K, Mitani K, Souma S, Kashiwagi S, Hebisawa A, Sato T, Kubo H, Gomi K, Shibuya K, Fukuchi Y, Suda K
  • Journal Title: Am J Surg Pathol. 29 Pages: 1356-1366
  • Peer Reviewed
• [Presentation] 大腸がんの肝転移における星細胞による誘導がん幹細胞(iCSC)の役割 (2009)
  • Author(s): 久保肇
  • Organizer: 第18回がん転移学会学術集会、シンポジウム
  • Place of Presentation: 旭川
  • Year and Date: 2009-07-23
• [Presentation] 消化器癌転移の新しい分子機構と新規治療法:リンパ管新生および癌幹細胞の研究 (2007)
  • Author(s): 久保肇
  • Organizer: 第62回日本消化器外科学会総会、シンポジウム
  • Place of Presentation: 福岡
  • Year and Date: 20070718-20070720
• [Presentation] リンパ管新生の分子機構とがんリンパ節転移 (2006)
  • Author(s): 久保肇
  • Organizer: 第8回Sentinel Node Navigation Surgery研究会学術集会、サテライトシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 20061117-20061118
• [Presentation] Lymphangiogenesis and cancer (2006)
  • Author(s): Kubo, H.
  • Organizer: The 11th International Congress of Metastasis Research Society, Plenary Sessions
  • Place of Presentation: Tokushima
  • Year and Date: 20060903-20060906
• [Presentation] リンパ管新生とがん転移 (2006)
  • Author(s): 久保肇
  • Organizer: 第30回日本リンパ学会、シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 20060601-20030603
• [Presentation] リンパ管新生と癌 (2006)
  • Author(s): 久保肇
  • Organizer: 第2回Summer Vascular Conference
  • Place of Presentation: 軽井沢
  • Year and Date: 2006-09-02
• [Presentation] リンパ管新生研究の新しい知見 (2005)
  • Author(s): 久保肇
  • Organizer: 第28回日本分子生物学会、シンポジウム
  • Place of Presentation: 福岡
  • Year and Date: 20051207-20051210
• [Presentation] ヒト癌細胞におけるホメオボックス遺伝子のRNA編集 (2005)
  • Author(s): 高橋めい子、吉本貴宣、久保肇
  • Organizer: 第64回日本癌学会、ポスター
  • Place of Presentation: 札幌
  • Year and Date: 20050914-20050916
• [Presentation] リンパ管新生の分子機構とがんリンパ節転移 (2005)
  • Author(s): 久保肇
  • Organizer: 第64回日本癌学会、シンポジウム
  • Place of Presentation: 札幌
  • Year and Date: 20050914-20050916
• [Presentation] がんとリンパ管;そしてリンパ管関連分子とがんについて (2005)
  • Author(s): 久保肇
  • Organizer: 第1回先端がん転移研究交流会
  • Place of Presentation: 鳴門
  • Year and Date: 20050819-20050820
• [Presentation] Recent progress in lymphangiogenesis research (2005)
  • Author(s): Kubo, H.
  • Organizer: Korea-Japan Joint Symposium Vascular Biology, Symposium
  • Place of Presentation: Chuncheon
  • Year and Date: 20050810-20050812
• [Presentation] リンパ管内皮細胞分化にかかわる分子 (2005)
  • Author(s): 久保肇
  • Organizer: 第29回日本リンパ学会、シンポジウム
  • Place of Presentation: 宇部
  • Year and Date: 20050715-20070717
• [Presentation] Differentiation of Lymphatic endothelial cells from ES cells (2005)
  • Author(s): 河野朋哉、久保肇
  • Organizer: AIM meeting, ポスター
  • Place of Presentation: 熊本
  • Year and Date: 20050519-20050521
• [Presentation] リンパ管新生の分子機構の解明とがんリンパ節転移制御 (2005)
  • Author(s): 久保肇
  • Organizer: 第78回日本薬理学会年会、シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 20050322-20050324
• [Presentation] Lymphangiogenesis and cancer (2005)
  • Author(s): Kubo, H.
  • Organizer: International Symposium on Tumor Biology in Kanazawa, Symposium
  • Place of Presentation: Kanazawa
  • Year and Date: 2005-01-20