Stromal factors regulating tumor cell motility

2009 Fiscal Year Final Research Report

• Project/Area Number: 17014056
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: MIYASAKA Masayuki Osaka University, 医学系研究科, 教授 (50064613)
• Co-Investigator(Kenkyū-buntansha): HAYASAKA Haruko 大阪大学, 医学系研究科, 助教 (70379246) ; UMEMOTO Eui 大阪大学, 医学系研究科, 助教 (90452440) ; JANG Myoung-ho 大阪大学, 免疫学フロンティア研究センター, 特任准教授(常勤) (70420453) ; BAI Zhongbin 大阪大学, 免疫学フロンティア研究センター, 特任研究員 (10512840) ; VERJAN-GARCIA Noel 大阪大学, 免疫学フロンティア研究センター, 特任研究員 (90533216) ; HIRATA Takako 京都大学, 医学研究科, 特定准教授 (00346199) ; TANAKA Toshiyuki 兵庫医療大学, 薬学部, 教授 (30217054)
• Project Period (FY): 2005 – 2009
• Keywords: 癌 / 糖鎖 / バイオテクノロジー / 免疫学 / 転移 / 細胞外基質 / 接着分子

Research Abstract

We have identified tumor stroma-derived molecules that upregulate tumor cell motility via cell surface CD44 ; they include low-molecular-weight hyaluronic acid and chondroitin sulfate E. They are produced by the enzymes produced by tumor cells and act on the tumor cells in an autocrine/paracrine manner. We also found that a number of the stroma-derived molecules bind chemokines and that certain combinations of chemokines modulate tumor cell motility, implying that certain stroma-derived molecules and chemokines upregulate tumor cell motility synergistically.

Research Products

• [Journal Article] Rap1 controls lymphocyte adhesion cascades and interstitial migration within lymph nodes in a RAPL-dependent and independent manner. (2010)
  • Author(s): *Ebisuno, Y., *Katagiri, K., Katakai, T., Ueda, Y., Nemoto, T., Inada, H., Nabekura, J., Okada, T., Kannagi, R., Tanaka, T., Miyasaka, M., Hogg, N., Kinashi, T. (*equal contribution)
  • Journal Title: Blood 115 Pages: 804-814
  • Peer Reviewed
• [Journal Article] A LIM domain-containing adaptor, leupaxin, localizes in focal adhesion and suppresses the integrin-induced tyrosine phosphorylation of paxillin. (2010)
  • Author(s): Tanaka, T., Moriwaki, K., Murata, S., Miyasaka, M.
  • Journal Title: Cancer Sci. 101 Pages: 363-368
  • Peer Reviewed
• [Journal Article] P-selectin glycoprotein ligand-1 negatively regulates T-cell immune responses. (2009)
  • Author(s): Matsumoto, M., Miyasaka, M., Hirata, T.
  • Journal Title: J. Immunol. 183 Pages: 7204-7211
  • Peer Reviewed
• [Journal Article] Involvement of chondroitin sulfate E in the liver tumor focal formation of murine osteosarcoma cells. (2009)
  • Author(s): Basappa, Murugan, S., Sugahara, K.N., Lee, C.M., ten Dam, G.B., van Kuppevelt, T.H., Miyasaka, M., Yamada, S., Sugahara, K.
  • Journal Title: Glycobiology 19 Pages: 735-742
  • Peer Reviewed
• [Journal Article] CXCL12 promotes CCR7-dependent naive T-cell trafficking to lymph nodes and Peyer's patches. (2009)
  • Author(s): *Bai, Z., *Hayasaka, H., Kobayashi, M., Li, W., Guo, Z., Jang, M.H., Kondo, A., Choi, B., Iwakura, Y., Miyasaka, M. (*equal contribution)
  • Journal Title: J. Immunol. 182 Pages: 1287-1295
  • Peer Reviewed
• [Journal Article] Nepmucin/CLM-9, an Ig domain-containing sialomucin in vascular endothelial cells, promotes lymphocyte transendothelial migration in vitro. (2008)
  • Author(s): Jin, S., Umemoto, E., Tanaka, T., Shimomura, Y., Tohya, K., Kunizawa, K., Yang, B. -G., Jang, M.H., Hirata, T., Miyasaka, M.
  • Journal Title: FEBS Lett. 582 Pages: 3018-3024
  • Peer Reviewed
• [Journal Article] Involvement of a lysophosphatidic-acid generating enzyme autotaxin in lymphocyte-endothelial cell interactions. (2008)
  • Author(s): *Nakasaki, T., *Tanaka, T., Okudaira, S., Hirosawa, M., Umemoto, E., Otani, K., Jin, S., Bai, Z., Hayasaka, H., Fukui, Y., Aozasa, K., Fujita, N., Tsuruo, T., Ozono, K., Aoki, J., Miyasaka, M. (*equal contribution)
  • Journal Title: Am. J. Pathol. 173 Pages: 1566-1576
  • Peer Reviewed
• [Journal Article] CD43 plays both antiadhesive and proadhesive roles in neutrophil rolling in a context-dependent manner. (2008)
  • Author(s): Matsumoto, M., Shigeta, A., Miyasaka, M., Hirata, T.
  • Journal Title: J. Immunol. 181 Pages: 3628-3635
  • Peer Reviewed
• [Journal Article] Chondroitin sulfate E fragments enhance CD44 cleavage and CD44-dependent motility in tumor cells. (2008)
  • Author(s): Sugahara, K.N., Hirata, T., Tanaka, T., Ogino, S., Takeda, M., Terasawa, H., Shimada, I., Tamura, J., Ten Dam, G.B., Van Kuppevelt, T.H., Miyasaka, M.
  • Journal Title: Cancer Res. 68 Pages: 7191-7199
  • Peer Reviewed
• [Journal Article] Identification of novel isoforms of mouse L-selectin with different carboxy-terminal tails. (2008)
  • Author(s): Furukawa, Y., Umemoto, E., Jang, M.H., Tohya, K., Miyasaka, M., Hirata, T.
  • Journal Title: J. Biol. Chem. 283 Pages: 12112-12119
  • Peer Reviewed
• [Journal Article] Binding of lymphoid chemokines to collagen IV that accumulates in the basal lamina of high endothelial venules; its implication in lymphocyte trafficking. (2007)
  • Author(s): Yang, B. -G., Tanaka, T., Jang, M.H., Bai, Z., Hayasaka, H., Miyasaka, M.
  • Journal Title: J. Immunol. 179 Pages: 4376-4382
  • Peer Reviewed
• [Journal Article] Plasmacytoid dendritic cells employ multiple cell adhesion molecules sequentially to interact with high endothelial venule cells - Molecular basis of their trafficking to lymph nodes. (2007)
  • Author(s): *Matsutani, T., *Tanaka, T., Tohya, K., Otani, K., Jang, M.H., Umemoto, E., Taniguchi, K., Hayasaka, H., Ueda, K., Miyasaka, M. (*equal contribution)
  • Journal Title: Int. Immunol. 19 Pages: 1031-1037
  • Peer Reviewed
• [Journal Article] CD43 collaborates with P-selectin glycoprotein ligand-1 to mediate E-selectin-dependent T cell migration into inflamed skin. (2007)
  • Author(s): Matsumoto, M., Shigeta, A., Furukawa, Y., Tanaka, T., Miyasaka, M., Hirata, T.
  • Journal Title: J. Immunol. 178 Pages: 2499-2506
  • Peer Reviewed
• [Journal Article] Ligand-induced structural changes of the CD44 hyaluronan-binding domain revealed by NMR. (2006)
  • Author(s): Takeda, M., Ogino, S., Umemoto, R., Sakakura, M., Kajiwara, M., Sugahara, K.N., Miyasaka, M., Terasawa, H., Shimada, I.
  • Journal Title: J. Biol. Chem. 281 Pages: 40089-40095
  • Peer Reviewed
• [Journal Article] Nepmucin, a novel HEV sialomucin, mediates L-selectin-dependent lymphocyte rolling and promotes lymphocyte adhesion under flow. (2006)
  • Author(s): Umemoto, E., Tanaka, T., Kanda, H., Jin, S., Tohya, K., Otani, K., Matsutani, T., Matsumoto, M., Ebisuno, Y., Jang, M.H., Fukuda, M., Hirata, T., Miyasaka, M.
  • Journal Title: J. Exp. Med. 203 Pages: 1603-1614
  • Peer Reviewed
• [Journal Article] Tumor cells enhance their own CD44 cleavage and motility by generating hyaluronan fragments. (2006)
  • Author(s): Sugahara, K.N., Hirata, T., Hayasaka, H., Stern, R., Murai, T., Miyasaka, M.
  • Journal Title: J. Biol. Chem. 281 Pages: 5861-5868
  • Peer Reviewed
• [Journal Article] Invasive human pancreatic carcinoma cells adhere to endothelial tri-cellular corners and increase endothelial permeability. (2005)
  • Author(s): Nakai, K., Tanaka, T., Murai, T., Ohguro, N., Tano, Y., Miyasaka, M.
  • Journal Title: Cancer Sci. 96 Pages: 766-773
  • Peer Reviewed
• [Journal Article] CXCL13 is an arrest chemokine for B cells in high endothelial venules. (2005)
  • Author(s): *Kanemitsu, N., *Ebisuno, Y., *Tanaka, T., Otani, K., Hayasaka, H., Kaisho, T., Akira, S., Katagiri, K., Kinashi, T., Fujita, N., Tsuruo, T., Miyasaka, M. (*equal contribution)
  • Journal Title: Blood 106 Pages: 2613-2618
  • Peer Reviewed
• [Journal Article] Chemokines in tumor progression and metastasis. (2005)
  • Author(s): Tanaka, T., Bai, Z., Srinoulprasert, Y., Yang, B. -G., Hayasaka, H., Miyasaka, M.: Review
  • Journal Title: Cancer Sci. 96 Pages: 317-322
  • Peer Reviewed
• [Presentation] CD44-mediated cell rolling regulated by two-state conformational equilibrium of the hyaluronan-binding domain. (2009)
  • Author(s): Suzuki, M., et al.
  • Organizer: The 39th Annual Meeting of the Japanese Society for Immunology. Dec.
  • Place of Presentation: Osaka
  • Year and Date: 20091202-20091204
• [Presentation] Characterization of CXCR4+ cells with prominent membrane blebbing in a human colon adenocarcinoma cell line LoVo. (2009)
  • Author(s): Matsumoto, M., et al.
  • Organizer: The 68th Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: Yokohama
  • Year and Date: 20091001-20091003
• [Presentation] Attempts to identify the cell population directly involved in invasion/metastasis in human malignant mesothelioma. (2009)
  • Author(s): Kubota, H., et al.
  • Organizer: The 68th Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: Yokohama
  • Year and Date: 20091001-20091003
• [Presentation] The E-type structure of chondroitin/dermatan sulfate on tumor cell surfaces is involved in lung and liver metastases. (2009)
  • Author(s): Sugahara, K., et al.
  • Organizer: 6th International Conference on Preteoglycan.
  • Place of Presentation: Aix-les-Bains, France
  • Year and Date: 20090913-20090917
• [Presentation] マウス癌細胞株の肺および肝臓への転移にはコンドロイチン硫酸E様構造が関与する. (2009)
  • Author(s): 菅原一幸, 他.
  • Organizer: 第29回日本糖質学会年会
  • Place of Presentation: 岐阜
  • Year and Date: 20090909-20090911
• [Presentation] 乳癌細胞におけるCXCL12とCCR7リガンド協働作用の解析. (2009)
  • Author(s): 早坂晴子, 他
  • Organizer: 第18回日本がん転移学会学術集会・総会
  • Place of Presentation: 旭川
  • Year and Date: 20090723-20090724
• [Presentation] The role of CD44-ECM interactions in tumor invasion. (2009)
  • Author(s): Miyasaka, M., et al.
  • Organizer: Yokosuka Science Festa 2009
  • Place of Presentation: Yokosuka
  • Year and Date: 20090604-20090607
• [Presentation] 癌細胞におけるCXCL12及びCCL19/CCL21の協働作用の検討. (2008)
  • Author(s): 岩本由希, 他
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 20081209-20081212
• [Presentation] 癌細胞の動態を制御する間質因子. (2008)
  • Author(s): 宮坂昌之
  • Organizer: 第49回日本肺癌学会総会
  • Place of Presentation: 福岡
  • Year and Date: 20081113-20091114
• [Presentation] Characterization of SP and non-SP in a human colon adenocarcinoma cell line LoVo. (2008)
  • Author(s): Nishiyama, M., et al.
  • Organizer: The 67th Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: Nagoya
  • Year and Date: 20081028-20081030
• [Presentation] A novel endothelial cell adhesion molecule, nepmucin: Its absence of expression in immunologically privileged sites and tumor tissues. (2008)
  • Author(s): Umemoto, E., et al.
  • Organizer: The U.S. - Japan Cooperative Cancer Research Program Workshop 2008
  • Place of Presentation: Kyoto
  • Year and Date: 20080319-20080321
• [Presentation] Nepmucin that shows homophilic binding plays a role in lymphocyte transmigration across vascular endothelial cells. (2007)
  • Author(s): Jin, S., et al.
  • Organizer: The 37th Annual Meeting of the Japanese Society for Immunology.
  • Place of Presentation: Tokyo
  • Year and Date: 20071120-20071122
• [Presentation] A novel endothelial cell adhesion molecule, nepmucin: Its absence of expression in immunologically privileged sites and tumor tissues. (2007)
  • Author(s): Umemoto, E., et al.
  • Organizer: Invited lecture. The 6th Sino-Japan Joint Conference for Cancer Research.
  • Place of Presentation: Toya
  • Year and Date: 20071006-20071007
• [Presentation] 癌細胞のケモタキシスにおけるケモカイン協働作用の解析. (2007)
  • Author(s): 早坂晴子, 他
  • Organizer: 第16回日本がん転移学会学術集会
  • Place of Presentation: 富山
  • Year and Date: 20070709-20070710
• [Patent(Industrial Property Rights)] 低分子コンドロイチン硫酸を含む医薬 (2005)
  • Inventor(s): 宮坂昌之、前田浩、村松信、松本太郎
  • Industrial Property Rights Holder: 大正製薬株式会社
  • Industrial Property Number: 特許・特願2005-150820
  • Filing Date: 2005-05-24