Proteomic analysis targeting stroma of pancreatic cancer

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592018
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Yokohama City University
• Principal Investigator: ENDO Itaru 横浜市立大学, 医学(系)研究科(研究院), 教授 (60211091)
• Co-Investigator(Kenkyū-buntansha): HIRANO Hisashi 横浜市立大学, 生命ナノシステム科学研究科, 教授 (00275075) ; MORI Ryutaro 横浜市立大学, 附属病院, 助教 (90596412) ; HIROSHIMA Yukihiko 横浜市立大学, 医学研究科, 客員研究員 (60718021)
• Project Period (FY): 2011 – 2013
• Keywords: 膵癌 / 癌微小環境 / 転移 / 浸潤

Research Abstract

Pancreatic cancer has an aggressive malignancy. Recently, stroma in tumor is reported to be associated with cancer-cell proliferation, apoptosis, differentiation and invasion in several cancers. In this project, we comprehensively examined proteins expressing in the stroma of pancreatic tumors or of normal pancreas, and found that CRMP4 differentially expressed in pancreatic tumor stroma compared to normal pancreatic tissue. Of all the CRMPs, only crmp4 was differentially expressed in pancreatic cancer tissues. CRMP4 staining was highly correlated with poor differentiation and liver metastasis. Multivariate analyses suggested that venous invasion and CRMP4 overexpression were prognostic factors for survival. CRMP4 knockdown using siRNA reduced cellular invasion, but did not affect proliferation. Our results suggested that CRMP4 is significantly associated with poor prognosis by increasing pancreatic cancer cell invasiveness, and can be a novel therapeutic target for pancreatic cancer.

Research Products

• [Journal Article] Hand-Held High-Resolution Fluorescence Imaging System for Fluorescence-Guided Surgery of Patient and Cell-Line Pancreatic Tumors Growing Orthotopically in Nude Mice (2013)
  • Author(s): Yukihiko Hiroshima, Ali Maawy, Sho Sato, Takashi Murakami, Fuminari Uehara, Shinji Miwa, Shuya Yano, Masashi Momiyama, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo and Robert M. Hoffman
  • Journal Title: J Surg Res. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Successful fluorescence-guided surgery on human colon cancer patient-derived orthotopic xenograft (PDOX) mouse models using a fluorophore-conjugated anti-CEA antibody and a portable imaging system (2013)
  • Author(s): Yukihiko Hiroshima, Ali Maawy, Cristina A. Metildi, Yong Zhang, Fuminari Uehara, Shinji Miwa, Shuya Yano, Sho Sato, Takashi Murakami, Masashi Momiyama, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo and Robert M. Hoffman
  • Journal Title: J Laparoendosc Adv Surg Tech A. Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Comparison of efficacy of Salmonella typhimurium A1-R and chemotherapy on stem-like and non-stem human pancreatic cancer cells (2013)
  • Author(s): Hiroshima Y, Zhao M, Zhang Y, Maawy A, Hassanein MK, Uehara F, Miwa S, Yano S, Momiyama M, Suetsugu A, Chishima T, Tanaka K, Bouvet M, Endo I, Hoffman RM.
  • Journal Title: Cell Cycle Volume: 12(17) Pages: 2774-80
  • DOI: 10.4161/cc.25872
  • Peer Reviewed
• [Journal Article] Collapsin Response Mediator Protein 4 Expression is Associated with Liver Metastasis and Poor Survival in Pancreatic Cancer (2013)
  • Author(s): Hiroshima Y, Nakamura F, Miyamoto H, Mori R, Taniguchi K, Matsuyama R, Akiyama H, Tanaka K, Ichikawa Y, Kato S, Kobayashi N, Kubota K, Nagashima Y, Goshima Y, Endo I.
  • Journal Title: Ann Surg Oncol Volume: 20 Suppl 3 Pages: S369-78
  • DOI: 10.1245/s10434-012-2491-3
  • Peer Reviewed
• [Presentation] Salmonella typhimurium A1-R effectively targets human-patient pancreatic tumorgrafts in nude mice (2013)
  • Author(s): Ming Zhao, Matthew H. G. Katz, Jason B. Fleming, Atsushi Suetsugu, Yong Zhang, Ali Maawy, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman, Yukihiko Hiroshima
  • Organizer: ASCO annual meeting
  • Place of Presentation: Chicago, IL
  • Year and Date: 20130531-0604
• [Presentation] Salmonella typhimurium A1-R targets chemoresistant stem-like human pancreatic cancer cells (2013)
  • Author(s): Yukihiko Hiroshima, Ming Zhao, Yong Zhang, Ali Maawy, Mohamed K. Hassanein, Atsushi Suetsugu, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman
  • Organizer: ASCO annual meeting
  • Place of Presentation: Chicago, IL
  • Year and Date: 20130531-0604
• [Presentation] Efficacy of Salmonella typhimurium A1-R on chemoresistant stem-like human pancreatic cancer cells (2013)
  • Author(s): Yukihiko Hiroshima, Ming Zhao, Yong Zhang, Ali Maawy, Mohamed Hassanein, Atsushi Suetsugu, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman
  • Organizer: AACR annual meeting
  • Place of Presentation: Washington, DC
  • Year and Date: 20130406-10
• [Presentation] Fluorescence-guided surgery for human-patient colon cancer tumorgrafts using a fluorophore-conjugated anti-CEA antibody (2013)
  • Author(s): Yukihiko Hiroshima, Ali Maawy, Yong Zhang, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman
  • Organizer: AACR annual meeting
  • Place of Presentation: Washington, DC
  • Year and Date: 20130406-10
• [Presentation] Tumor-educated macrophages promote proliferation of human pancreatic cancer cells in vitro and in vivo (2013)
  • Author(s): Yukihiko Hiroshima, Masashi Momiyama, Mohamed Hassanein, Ali Maawy, Rhiana Menen, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman
  • Organizer: AACR annual meeting
  • Place of Presentation: Washington, DC
  • Year and Date: 20130406-10
• [Presentation] Efficacy of Salmonella typhimurium A1-R treatment on human patient pancreatic tumorgrafts (2013)
  • Author(s): Yukihiko Hiroshima, Ming Zhao, Matthew H.G. Katz, Jason B. Fleming, Atsushi Suetsugu, Yong Zhang, Ali Maawy, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman
  • Organizer: AACR annual meeting
  • Place of Presentation: Washington, DC
  • Year and Date: 20130406-10
• [Presentation] Collapsin response mediator protein 4 promotes tumor cell invasion and lethality of pancreatic cancer (2012)
  • Author(s): Yukihiko Hiroshima, Fumio Nakamura, Hiroshi Miyamoto, Ryutaro Mori, Koichi Taniguchi, Ryusei Matsuyama, Kazuhisa Takeda, Hirotoshi Akiyama, Kuniya Tanaka, Yasushi Ichikawa, Yoji Nagashima, Yoshio Goshima, Itaru Endo
  • Organizer: AACR annual meeting
  • Place of Presentation: Chicago, IL
  • Year and Date: 20120331-0404
• [Remarks]
  • URL: http://www.ycusurg2.jp/index.html