Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
July-2014 Volume 45 Issue 1

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July-2014 Volume 45 Issue 1

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer

  • Authors:
    • Shin Akagawa
    • Kenoki Ohuchida
    • Nobuhiro Torata
    • Masami Hattori
    • Daiki Eguchi
    • Kenji Fujiwara
    • Shingo Kozono
    • Lin Cui
    • Naoki Ikenaga
    • Takao Ohtsuka
    • Shinichi Aishima
    • Kazuhiro Mizumoto
    • Yoshinao Oda
    • Masao Tanaka
  • View Affiliations / Copyright

    Affiliations: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  • Pages: 113-120
    |
    Published online on: April 16, 2014
       https://doi.org/10.3892/ijo.2014.2391
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Myofibroblasts in the stroma of pancreatic cancers promote tumor proliferation, invasion and metastasis by increasing extracellular matrix and secretion of several growth factors. In contrast, the role of myofibroblasts at peritoneally disseminated sites of pancreatic cancer has not yet been determined. This study was designed to assess the role of myofibroblasts at peritoneally disseminated sites of pancreatic cancer. Three primary cultures of human peritoneal myofibroblasts (hPMFs) were established from disseminated sites of pancreatic cancer and their interactions with the SUIT-2 and CAPAN-1 human pancreatic cancer cell lines were analyzed in vitro. Using a model in BALB/c nu/nu mice, we compared the dissemination ability of intraperitoneally implanted pancreatic cancer cells, with and without hPMFs, and examined the presence of green fluorescent protein (GFP)-labeled hPMFs at peritoneally disseminated sites in mice. hPMFs significantly promoted the migration and invasion of pancreatic cancer cells (P<0.05), while the cancer cells significantly promoted the migration and invasion of hPMFs (P<0.05). In vivo, the number of peritoneally disseminated nodules, more than 3 mm in size, was significantly greater in mice implanted with cancer cells plus hPMFs compared to mice implanted with cancer cells alone, with GFP-labeled hPMFs surviving in the peritoneal cavity of the former. hPMFs promote the peritoneal dissemination of pancreatic cancer. The cancer-stromal cell interaction in the peritoneal cavity may be a new therapeutic target to prevent the dissemination of pancreatic cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1. 

Vincent A, Herman J, Schulick R, Hruban RH and Goggins M: Pancreatic cancer. Lancet. 378:607–620. 2011. View Article : Google Scholar

2. 

Sener SF, Fremgen A, Menck HR and Winchester DP: Pancreatic cancer: A report of treatment and survival trends for 100,313 patients diagnosed from 1985–1995, using the National Cancer Database. J Am Coll Surg. 189:1–7. 1999.PubMed/NCBI

3. 

Chu DZ, Lang NP, Thompson C, Osteen PK and Westbrook KC: Peritoneal carcinomatosis in nongynecologic malignancy. A prospective study of prognostic factors. Cancer. 63:364–367. 1989. View Article : Google Scholar : PubMed/NCBI

4. 

Sadeghi B, Arvieux C, Glehen O, et al: Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study. Cancer. 88:358–363. 2000. View Article : Google Scholar : PubMed/NCBI

5. 

Armstrong T, Packham G, Murphy LB, et al: Type I collagen promotes the malignant phenotype of pancreatic ductal adenocarcinoma. Clin Cancer Res. 10:7427–7437. 2004. View Article : Google Scholar : PubMed/NCBI

6. 

Mahadevan D and Von Hoff DD: Tumor-stroma interactions in pancreatic ductal adenocarcinoma. Mol Cancer Ther. 6:1186–1197. 2007. View Article : Google Scholar : PubMed/NCBI

7. 

Feig C, Gopinathan A, Neesse A, Chan DS, Cook N and Tuveson DA: The pancreas cancer microenvironment. Clin Cancer Res. 18:4266–4276. 2012. View Article : Google Scholar : PubMed/NCBI

8. 

Hwang RF, Moore T, Arumugam T, et al: Cancer-associated stromal fibroblasts promote pancreatic tumor progression. Cancer Res. 68:918–926. 2008. View Article : Google Scholar

9. 

Apte MV, Park S, Phillips PA, et al: Desmoplastic reaction in pancreatic cancer: role of pancreatic stellate cells. Pancreas. 29:179–187. 2004. View Article : Google Scholar : PubMed/NCBI

10. 

Joyce JA and Pollard JW: Microenvironmental regulation of metastasis. Nat Rev Cancer. 9:239–252. 2009. View Article : Google Scholar

11. 

Strell C, Rundqvist H and Ostman A: Fibroblasts - a key host cell type in tumor initiation, progression, and metastasis. Ups J Med Sci. 117:187–195. 2012. View Article : Google Scholar : PubMed/NCBI

12. 

Fujita H, Ohuchida K, Mizumoto K, et al: Tumor-stromal interactions with direct cell contacts enhance proliferation of human pancreatic carcinoma cells. Cancer Sci. 100:2309–2317. 2009. View Article : Google Scholar : PubMed/NCBI

13. 

Yashiro M, Chung YS, Nishimura S, Inoue T and Sowa M: Fibrosis in the peritoneum induced by scirrhous gastric cancer cells may act as ‘soil’ for peritoneal dissemination. Cancer. 77:1668–1675. 1996.PubMed/NCBI

14. 

Cai J, Tang H, Xu L, et al: Fibroblasts in omentum activated by tumor cells promote ovarian cancer growth, adhesion and invasiveness. Carcinogenesis. 33:20–29. 2012. View Article : Google Scholar : PubMed/NCBI

15. 

Peron JM, Bureau C, Gourdy P, et al: Treatment of experimental murine pancreatic peritoneal carcinomatosis with fibroblasts genetically modified to express IL12: a role for peritoneal innate immunity. Gut. 56:107–114. 2007. View Article : Google Scholar

16. 

Yanez-Mo M, Lara-Pezzi E, Selgas R, et al: Peritoneal dialysis and epithelial-to-mesenchymal transition of mesothelial cells. N Engl J Med. 348:403–413. 2003. View Article : Google Scholar : PubMed/NCBI

17. 

Tsukada T, Fushida S, Harada S, et al: The role of human peritoneal mesothelial cells in the fibrosis and progression of gastric cancer. Int J Oncol. 41:476–482. 2012.PubMed/NCBI

18. 

Epperly MW, Guo H, Gretton JE and Greenberger JS: Bone marrow origin of myofibroblasts in irradiation pulmonary fibrosis. Am J Respir Cell Mol Biol. 29:213–224. 2003. View Article : Google Scholar : PubMed/NCBI

19. 

Xu Z, Vonlaufen A, Phillips PA, et al: Role of pancreatic stellate cells in pancreatic cancer metastasis. Am J Pathol. 177:2585–2596. 2010. View Article : Google Scholar : PubMed/NCBI

20. 

Krist LF, Kerremans M, Broekhuis-Fluitsma DM, Eestermans IL, Meyer S and Beelen RH: Milky spots in the greater omentum are predominant sites of local tumour cell proliferation and accumulation in the peritoneal cavity. Cancer Immunol Immunother. 47:205–212. 1998. View Article : Google Scholar

21. 

Mochizuki Y, Nakanishi H, Kodera Y, et al: TNF-alpha promotes progression of peritoneal metastasis as demonstrated using a green fluorescence protein (GFP)-tagged human gastric cancer cell line. Clin Exp Metastasis. 21:39–47. 2004. View Article : Google Scholar : PubMed/NCBI

22. 

Sorensen EW, Gerber SA, Sedlacek AL, Rybalko VY, Chan WM and Lord EM: Omental immune aggregates and tumor metastasis within the peritoneal cavity. Immunol Res. 45:185–194. 2009. View Article : Google Scholar : PubMed/NCBI

23. 

Tsujimoto H, Takhashi T, Hagiwara A, et al: Site-specific implantation in the milky spots of malignant cells in peritoneal dissemination: immunohistochemical observation in mice inoculated intraperitoneally with bromodeoxyuridine-labelled cells. Br J Cancer. 71:468–472. 1995. View Article : Google Scholar

24. 

Sugarbaker PH: Peritoneum as the first-line of defense in carcinomatosis. J Surg Oncol. 95:93–96. 2007. View Article : Google Scholar : PubMed/NCBI

25. 

Yashiro M, Chung YS, Inoue T, et al: Hepatocyte growth factor (HGF) produced by peritoneal fibroblasts may affect mesothelial cell morphology and promote peritoneal dissemination. Int J Cancer. 67:289–293. 1996. View Article : Google Scholar : PubMed/NCBI

26. 

Bachem MG, Schneider E, Gross H, et al: Identification, culture, and characterization of pancreatic stellate cells in rats and humans. Gastroenterology. 115:421–432. 1998. View Article : Google Scholar : PubMed/NCBI

27. 

Bachem MG, Schunemann M, Ramadani M, et al: Pancreatic carcinoma cells induce fibrosis by stimulating proliferation and matrix synthesis of stellate cells. Gastroenterology. 128:907–921. 2005. View Article : Google Scholar : PubMed/NCBI

28. 

Jorres A, Ludat K, Lang J, et al: Establishment and functional characterization of human peritoneal fibroblasts in culture: regulation of interleukin-6 production by proinflammatory cytokines. J Am Soc Nephrol. 7:2192–2201. 1996.PubMed/NCBI

29. 

Ohuchida K, Mizumoto K, Murakami M, et al: Radiation to stromal fibroblasts increases invasiveness of pancreatic cancer cells through tumor-stromal interactions. Cancer Res. 64:3215–3222. 2004. View Article : Google Scholar : PubMed/NCBI

30. 

Ikenaga N, Ohuchida K, Mizumoto K, et al: CD10+ pancreatic stellate cells enhance the progression of pancreatic cancer. Gastroenterology. 139:1041–1051. 2010.

31. 

Sato N, Maehara N, Mizumoto K, et al: Telomerase activity of cultured human pancreatic carcinoma cell lines correlates with their potential for migration and invasion. Cancer. 91:496–504. 2001. View Article : Google Scholar : PubMed/NCBI

32. 

Yashiro M, Chung YS, Nishimura S, Inoue T and Sowa M: Peritoneal metastatic model for human scirrhous gastric carcinoma in nude mice. Clin Exp Metastasis. 14:43–54. 1996. View Article : Google Scholar : PubMed/NCBI

33. 

Lv ZD, Na D, Ma XY, Zhao C, Zhao WJ and Xu HM: Human peritoneal mesothelial cell transformation into myofibroblasts in response to TGF-β1 in vitro. Int J Mol Med. 27:187–193. 2011.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Akagawa S, Ohuchida K, Torata N, Hattori M, Eguchi D, Fujiwara K, Kozono S, Cui L, Ikenaga N, Ohtsuka T, Ohtsuka T, et al: Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer. Int J Oncol 45: 113-120, 2014.
APA
Akagawa, S., Ohuchida, K., Torata, N., Hattori, M., Eguchi, D., Fujiwara, K. ... Tanaka, M. (2014). Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer. International Journal of Oncology, 45, 113-120. https://doi.org/10.3892/ijo.2014.2391
MLA
Akagawa, S., Ohuchida, K., Torata, N., Hattori, M., Eguchi, D., Fujiwara, K., Kozono, S., Cui, L., Ikenaga, N., Ohtsuka, T., Aishima, S., Mizumoto, K., Oda, Y., Tanaka, M."Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer". International Journal of Oncology 45.1 (2014): 113-120.
Chicago
Akagawa, S., Ohuchida, K., Torata, N., Hattori, M., Eguchi, D., Fujiwara, K., Kozono, S., Cui, L., Ikenaga, N., Ohtsuka, T., Aishima, S., Mizumoto, K., Oda, Y., Tanaka, M."Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer". International Journal of Oncology 45, no. 1 (2014): 113-120. https://doi.org/10.3892/ijo.2014.2391
Copy and paste a formatted citation
x
Spandidos Publications style
Akagawa S, Ohuchida K, Torata N, Hattori M, Eguchi D, Fujiwara K, Kozono S, Cui L, Ikenaga N, Ohtsuka T, Ohtsuka T, et al: Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer. Int J Oncol 45: 113-120, 2014.
APA
Akagawa, S., Ohuchida, K., Torata, N., Hattori, M., Eguchi, D., Fujiwara, K. ... Tanaka, M. (2014). Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer. International Journal of Oncology, 45, 113-120. https://doi.org/10.3892/ijo.2014.2391
MLA
Akagawa, S., Ohuchida, K., Torata, N., Hattori, M., Eguchi, D., Fujiwara, K., Kozono, S., Cui, L., Ikenaga, N., Ohtsuka, T., Aishima, S., Mizumoto, K., Oda, Y., Tanaka, M."Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer". International Journal of Oncology 45.1 (2014): 113-120.
Chicago
Akagawa, S., Ohuchida, K., Torata, N., Hattori, M., Eguchi, D., Fujiwara, K., Kozono, S., Cui, L., Ikenaga, N., Ohtsuka, T., Aishima, S., Mizumoto, K., Oda, Y., Tanaka, M."Peritoneal myofibroblasts at metastatic foci promote dissemination of pancreatic cancer". International Journal of Oncology 45, no. 1 (2014): 113-120. https://doi.org/10.3892/ijo.2014.2391
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team