Proteomic analysis targeting stroma of pancreatic cancer

• 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
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 膵癌 / 癌微小環境 / 転移 / 浸潤 / ノックアウトマウス / 膵炎 / リン酸化 / 間質 / イメージング

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. (2014)
  • Author(s): Hiroshima Y, Maawy A, Sato S, Murakami T, Uehara F, Miwa S, Yano S, Momiyama M, Chishima T, Tanaka K, Bouvet M, Endo I, Hoffman RM.
  • Journal Title: J Surg Res. Volume: 187(2) Issue: 2 Pages: 510-7
  • DOI: 10.1016/j.jss.2013.11.1083
  • Peer Reviewed
• [Journal Article] Efficacy of Salmonella typhimurium A1-R Versus Chemotherapy on a Pancreatic Cancer Patient-Derived Orthotopic Xenograft (PDOX). (2014)
  • Author(s): Hiroshima Y, Zhao M, Maawy A, Zhang Y, Katz MH, Fleming JB, Uehara F, Miwa S, Yano S, Momiyama M, Suetsugu A, Chishima T, Tanaka K, Bouvet M, Endo I, Hoffman RM.
  • Journal Title: J Cell Biochem Volume: 115(7) Issue: 7 Pages: 1254-61
  • DOI: 10.1002/jcb.24769
  • Peer Reviewed
• [Journal Article] Successful fluorescence-guided surgery on human colon cancer patient-derived orthotopic xenograft mouse models using a fluorophore-conjugated anti-CEA antibody and a portable imaging system. (2014)
  • Author(s): Hiroshima Y, Maawy A, Metildi CA, Zhang Y, Uehara F, Miwa S, Yano S, Sato S, Murakami T, Momiyama M, Chishima T, Tanaka K, Bouvet M, Endo I, Hoffman RM.
  • Journal Title: J Laparoendosc Adv Surg Tech A. Volume: 24(4) Issue: 4 Pages: 241-7
  • DOI: 10.1089/lap.2013.0418
  • Peer Reviewed
• [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: 1;12(17) Issue: 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, Nagashima Y et al
  • Journal Title: Ann Surg Oncol Volume: 20 (Suppl 3) Issue: S3 Pages: 369-378
  • DOI: 10.1245/s10434-012-2491-3
  • Peer Reviewed
• [Journal Article] Collapsin Response Mediator Protein 4 Expression is Associated with Liver Metastasis and Poor Survival in Pancreatic Cancer. (2012)
  • Author(s): Hiroshima Yukihiko
  • Journal Title: Annals of Surgical Oncology Volume: -
  • Peer Reviewed
• [Presentation] Establishment of a patient-derived orthotopic xenograft (PDOX) model of patient cervical cancer (2014)
  • Author(s): Yukihiko Hiroshima1, Yong Zhang1, Ali Maawy2, Sho Sato3, Takashi Murakami3, Mako Yamamoto1, Fuminari Uehara1, Shinji Miwa1, Shuya Yano1, Masashi Momiyama3, Takashi Chishima3, Kuniya Tanaka3, Ali Maawy2, Itaru Endo3, Robert M. Hoffman1.
  • Organizer: AACR
  • Place of Presentation: San Diego, USA
• [Presentation] The advantages of patient-derived orthotopic xenograft (PDOX) of metastatic cervical cancer for individualized therapy compared to the PDX model (2014)
  • Author(s): Yukihiko Hiroshima1, Yong Zhang1, Ali Maawy2, Sho Sato3, Takashi Murakami3, Mako Yamamoto1, Fuminari Uehara1, Shinji Miwa1, Shuya Yano1, Masashi Momiyama3, Takashi Chishima3, Kuniya Tanaka3, Michael Bouvet2, Itaru Endo3, Robert M. Hoffman1.
  • Organizer: AACR
  • Place of Presentation: San Diego, USA
• [Presentation] Efficacy of Salmonella typhimurium A1-R and anti-VEGF therapy on a patient-derived orthotopic xenograft (PDOX) pancreatic cancer model (2014)
  • Author(s): Yukihiko Hiroshima1, Ming Zhao1, Matthew H.G. Katz2, Jason B. Fleming2, Sho Sato3, Takashi Murakami3, Mako Yamamoto1, Fuminari Uehara1, Shinji Miwa1, Shuya Yano1, Masashi Momiyama3, Yong Zhang1, Ali Maawy4, Takashi Chishima3, Kuniya Tanaka3, Michael Bouvet4, Itaru Endo3, Robert M. Hoffman1.
  • Organizer: AACR
  • Place of Presentation: San Diego, USA
• [Presentation] Zoledronic acid inhibits proliferation and metastasis of human pancreatic cancer in the patient-derived orthotopic xenograft (PDOX) model by targeting tumor-educated macrophages (2014)
  • Author(s): Yukihiko Hiroshima1, Mohamed K. Hassenein1, Rhiana Menen1, Matthew H.g. Katz2, Jason B. Fleming2, Sho Sato3, Takashi Murakami3, Mako Yamamoto1, Fuminari Uehara1, Shinji Miwa1, Shuya Yano1, Masashi Momiyama3, Ali Maawy4, Takashi Chishima3, Kuniya Tanaka3, Michael Bouvet4, Itaru Endo3, Robert M. Hoffman1.
  • Organizer: AACR
  • Place of Presentation: San Diego, USA
• [Presentation] Efficacy of neoadjuvant chemotherapy in combination with fluorescence-guided surgery on a pancreatic cancer patient-derived orthotopic xenograft (PDOX) (2014)
  • Author(s): Yukihiko Hiroshima1, Ali Maawy1, Yong Zhang1, Sho Sato2, Takashi Murakami2, Mako Yamamoto1, Fuminari Uehara1, Shinji Miwa1, Shuya Yano1, Masashi Momiyama2, Takashi Chishima2, Kuniya Tanaka2, Michael Bouvet3, Itaru Endo2, Robert M. Hoffman1.
  • Organizer: AACR
  • Place of Presentation: San Diego, USA
• [Presentation] UVC irradiation in combination with fluorescence-guided surgery cures metastatic human pancreatic cancer in orthotopic mouse models (2014)
  • Author(s): Yukihiko Hiroshima1, Ali Maawy2, Sho Sato3, Takashi Murakami3, Mako Yamamoto1, Fuminari Uehara1, Shinji Miwa1, Shuya Yano1, Masashi Momiyama3, Takashi Chishima3, Kuniya Tanaka3, Michael Bouvet4, Itaru Endo3, Robert M. Hoffman1.
  • Organizer: AACR
  • Place of Presentation: San Diego, USA
• [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
• [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
• [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
• [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
• [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
• [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
• [Presentation] Efficacy of Salmonella typhimurium A1-R on chemoresistant stem-like human pancreatic cancer cells (2013)
  • Author(s): Hiroshima Yukihiko
  • Organizer: AACR annual meeting
  • Place of Presentation: U.S.A., Washington, DC
• [Presentation] Fluorescence-guided surgery for human-patient colon cancer tumorgrafts using a fluorophore-conjugated anti-CEA antibody (2013)
  • Author(s): Hiroshima Yukihiko
  • Organizer: AACR annual meeting
  • Place of Presentation: U.S.A., Washington, DC
• [Presentation] Tumor-educated macrophages promote proliferation of human pancreatic cancer cells in vitro and in vivo (2013)
  • Author(s): Hiroshima Yukihiko
  • Organizer: AACR annual meeting
  • Place of Presentation: U.S.A., Washington, DC
• [Presentation] Efficacy of Salmonella typhimurium A1-R treatment on human patient pancreatic tumorgrafts (2013)
  • Author(s): Hiroshima Yukihiko
  • Organizer: AACR annual meeting
  • Place of Presentation: U.S.A., Washington, DC
• [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
• [Presentation] Collapsin Response Mediator Protein 4 Promotes Tumor Cell Invasion and Lethality of Pancreatic Cancer (2012)
  • Author(s): 廣島 幸彦
  • Organizer: AACR Annual Meeting 2012
  • Place of Presentation: アメリカ、シカゴ
• [Remarks]
  • URL: http://www.ycusurg2.jp/index.html