Functional analysis of the ER stress response in the development of lung cancer metastasis

• Project/Area Number: 21790775
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Respiratory organ internal medicine
• Research Institution: Kumamoto University
• Principal Investigator: ENDO Motoyoshi Kumamoto University, 大学院・生命科学研究部, 助教 (40398243)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 肺癌 / 転移 / 血管新生 / 小胞体ストレス / 血管新生因子 / 浸潤・転移 / アンジオポエチン様因子 / 低酸素・低栄養 / Angpt12 / サイトカイン / アポトーシス

Research Abstract

We examined the involvement of ER stress response in the development of lung metastases by using human lung cancer cell lines. High metastatic strain had high susceptibility to ER stress compared to low metastatic strain. From these results, high metastatic starin might take advantage of ER stress pathway for development of metastasis. In addition, we found that Angptl, which was an angiogenic and lymphangiogenic factor, was induced by ER stress stimuli. From these results, we supposed Angptl induced by ER stress response developed favorable environments for tumor invasion and metastasis.

Research Products

• [Journal Article] C/EBP Homologous Protein Deficiency Attenuates Myocardial Reperfusion Injury by Inhibiting Myocardial Apoptosis and Inflammation. (2010)
  • Author(s): Miyazaki Y, Kaikita K, Endo M, Horio E, Miura M, Tsujita K, Hokimoto S, Yamamuro M, Iwawaki T, Gotoh T, Ogawa H, Oike Y.
  • Journal Title: Arterioscler Thromb.Vasc.Biol. 31 Pages: 1124-1132
  • Peer Reviewed
• [Journal Article] The endoplasmic reticulum stress-C/EBP homologous protein pathway-mediated apoptosis in macrophages contributes to the instability of atherosclerotic plaques. (2010)
  • Author(s): Tsukano H, Gotoh T, Endo M, Miyata K, Tazume H, Kadomatsu T, Yano M, Iwawaki T, Kohno K, Araki K, Mizuta H, Oike Y.
  • Journal Title: Arterioscler Thromb.Vasc.Biol. 30 Pages: 1925-1932
  • Peer Reviewed
• [Journal Article] Synoviocyte-derived angiopoietin-like protein 2 contributes to synovial chronic inflammation in rheumatoid arthritis. (2010)
  • Author(s): Okada T, Tsukano H, Endo M, Tabata M, Miyata K, Kadomatsu T, Miyashita K, Semba K, Nakamura E, Tsukano M, Mizuta H, Oike Y.
  • Journal Title: Am.J.Pathol. 176 Pages: 2309-2319
  • Peer Reviewed
• [Journal Article] Molecular Mechanisms of the LPS-induced Non-apoptotic ER Stress-CHOP Pathway. (2010)
  • Author(s): Nakayama Y, Endo M, Tsukano H, Mori M, Oike Y, Gotoh T.
  • Journal Title: J.Biochem. 147 Pages: 471-483
  • NAID: 10027874883
  • Peer Reviewed
• [Journal Article] C/EBP Homologous Protein Deficiency Attenuates Myocardial Reperfusion Injury by Inhibiting Myocardial Apoptosis and Inflammation. (2010)
  • Author(s): Miyazaki Y., et.al.
  • Journal Title: Arterioscler.Thromb.Vasc.Biol. Volume: 30 Pages: 1925-1932
  • Peer Reviewed
• [Journal Article] The Endoplasmic Reticulum Stress-CHOP Pathway-mediated Apoptosis in Macrophages Contributes to the Instability of Atherosclerotic Plaques. (2010)
  • Author(s): Tsukano H., et.al.
  • Journal Title: Arterioscler.Thromb.Vasc.Biol. Volume: 30 Pages: 1925-1935
  • Peer Reviewed
• [Journal Article] Molecular mechanisms of the LPS-induced non-apoptotic ER stress-CHOP pathway. (2010)
  • Author(s): Nakayama Y, Endo M, et. al.
  • Journal Title: J.Biochem. 147 Pages: 471-483
  • NAID: 10027874883
  • Peer Reviewed
• [Journal Article] Synoviocyte-Derived Angiopoietin-Like Protein 2 Contributes to Synovial Chronic Inflammation in Rheumatoid Arthritis. (2010)
  • Author(s): Okada T., et. al.
  • Journal Title: Am.J.Pathol. 19(in press)
  • Peer Reviewed
• [Journal Article] Endoplasmic Reticulum Stress-induced Transcriptional Factor CHOP and Cardiovascular Diseases. (2009)
  • Author(s): Tomomi Gotoh, Motoyoshi Endo, Yuichi Oike
  • Journal Title: Current Hypertension Reviews 6 Pages: 55-65
  • Peer Reviewed
• [Journal Article] Angiopoietin-like protein 2 promotes chronic adipose tissue inflammation and obesity-related systemic insulin resistance. (2009)
  • Author(s): Tabata M, Kadomatsu T, Fukuhara S, Miyata K, Ito Y, Endo M, Urano T, Zhu HJ, Tsukano H, Tazume H, Kaikita K, Miyashita K, Iwawaki T, Shimabukuro M, Sakaguchi K, Ito T, Nakagata N, Yamada T, Katagiri H, Kasuga M, Ando Y, Ogawa H, Mochizuki N, Itoh H, Suda T, Oike Y.
  • Journal Title: Cell Metab. 10 Pages: 178-188
  • Peer Reviewed
• [Journal Article] Humanized anti-interleukin-6 receptor antibody suppresses tumor angiogenesis and in vivo growth of human oral squamous cell carcinoma. (2009)
  • Author(s): Shinriki S, Jono H, Ota K, Ueda M, Kudo M, Ota T, Oike Y, Endo M, Ibusuki M, Hiraki A, Nakayama H, Yoshitake Y, Shinohara M, Ando Y.
  • Journal Title: Clin.Cancer Res. 15 Pages: 5426-5434
  • Peer Reviewed
• [Journal Article] Angiopoietins contribute to lung development by regulating pulmonary vascular network formation. (2009)
  • Author(s): Hato T, Kimura Y, Morisada T, Koh GY, Miyata K, Tabata M, Kadomatsu T, Endo M, Urano T, Arai F, Araki K, Suda T, Kobayashi K, Oike Y.
  • Journal Title: Biochem.Biophys.Res.Commun. 381 Pages: 218-223
  • Peer Reviewed
• [Journal Article] Positive role of CCAAT/enhancer-binding protein homologous protein, a transcription factor involved in the endoplasmic reticulum stress response in the development of colitis. (2009)
  • Author(s): Namba T, Tanaka K, Ito Y, Ishihara T, Hoshino T, Gotoh T, Endo M, Sato K, Mizushima T.
  • Journal Title: Am.J.Pathol. 174 Pages: 1786-1798
  • Peer Reviewed
• [Journal Article] Angiopoietin-like protein 2 promotes chronic adipose tissue inflammation and obesity-related systemic insulin resistance. (2009)
  • Author(s): Tabata M., et. al.
  • Journal Title: Cell Metab. 10 Pages: 178-188
  • Peer Reviewed
• [Presentation] 肺癌の浸潤・転移におけるアンジオポエチン様因子2の機能解析 (2010)
  • Author(s): 遠藤元誉
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-24
• [Presentation] 肺癌の浸潤・転移におけるアンジオポエチン様因子2の機能解析 (2010)
  • Author(s): 遠藤元誉
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2010-09-24
• [Remarks]
  • URL: http://www.medphas.kumamoto-u.ac.jp/research/bunya/46.html