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
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
July-2015 Volume 34 Issue 1

Full Size Image

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-2015 Volume 34 Issue 1

Full Size Image

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

Downregulation of CD9 promotes pancreatic cancer growth and metastasis through upregulation of epidermal growth factor on the cell surface

  • Authors:
    • Maochun Tang
    • Guojian Yin
    • Feng Wang
    • Hua Liu
    • Shu Zhou
    • Jianbo Ni
    • Congying Chen
    • Yingqun Zhou
    • Yan Zhao
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China
  • Pages: 350-358
    |
    Published online on: May 7, 2015
       https://doi.org/10.3892/or.2015.3960
  • 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

The expression of CD9 has been shown to be inversely associated with pancreatic cancer metastasis but the underlying mechanism remains incompletely understood. Using the two closely associated pancreatic cancer cell lines, PaTu-8898s and PaTu-8898t, which are metastatic and non‑metastatic, respectively, we showed that the PaTu-8988s cells expressed a lower level of CD9 but had higher proliferation and migration rates than the PaTu-8898t cells. An inverse correlation between CD9 expression and the cell surface level of epidermal growth factor receptor (EGFR) was observed in both cell lines. In the PaTu-8898s cells, overexpression of CD9 decreased the cell surface expression of EGFR, associated with increased expression of dynamin-2, whereas in the PaTu-8898t cells, knockdown of CD9 with RNA interference (RNAi) increased the cell surface expression of EGFR, associated with decreased expression of dynamin-2. However, the total EGFR level did not change by manipulation of CD9 expression, suggesting that CD9 plays a role in EGFR endocytosis. Furthermore, in the PaTu-8898ts cells, CD9 overexpression decreased the cell proliferation and migration, which were reversed by EGFR overexpression, whereas in the PaTu-8898t cells, CD9 knockdown enhanced the cell proliferation and migration which were blocked by EGFR RNAi both in vitro and in vivo. Thus, in pancreatic cancer cells, downregulation of CD9 may play a role in cancer growth and metastasis through, at least in part, enhancing cell surface expression of EGFR.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Hezel AF, Kimmelman AC, Stanger BZ, Bardeesy N and Depinho RA: Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev. 20:1218–1249. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Wray CJ, Ahmad SA, Matthews JB and Lowy AM: Surgery for pancreatic cancer: Recent controversies and current practice. Gastroenterology. 128:1626–1641. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Jemal A, Siegel R, Ward E, Hao Y, Xu J and Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 59:225–249. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Breslin TM, Hess KR, Harbison DB, Jean ME, Cleary KR, Dackiw AP, Wolff RA, Abbruzzese JL, Janjan NA, Crane CH, et al: Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: Treatment variables and survival duration. Ann Surg Oncol. 8:123–132. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Maecker HT, Todd SC and Levy S: The tetraspanin superfamily: Molecular facilitators. FASEB J. 11:428–442. 1997.PubMed/NCBI

6 

Berditchevski F: Complexes of tetraspanins with integrins: More than meets the eye. J Cell Sci. 114:4143–4151. 2001.PubMed/NCBI

7 

Boucheix C and Rubinstein E: Tetraspanins. Cell Mol Life Sci. 58:1189–1205. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Hemler ME: Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain. Annu Rev Cell Dev Biol. 19:397–422. 2003. View Article : Google Scholar : PubMed/NCBI

9 

Shaw AR, Domanska A, Mak A, Gilchrist A, Dobler K, Visser L, Poppema S, Fliegel L, Letarte M and Willett BJ: Ectopic expression of human and feline CD9 in a human B cell line confers beta 1 integrin-dependent motility on fibronectin and laminin substrates and enhanced tyrosine phosphorylation. J Biol Chem. 270:24092–24099. 1995. View Article : Google Scholar : PubMed/NCBI

10 

Jones PH, Bishop LA and Watt FM: Functional significance of CD9 association with beta 1 integrins in human epidermal keratinocytes. Cell Adhes Commun. 4:297–305. 1996. View Article : Google Scholar : PubMed/NCBI

11 

Inui S, Higashiyama S, Hashimoto K, Higashiyama M, Yoshikawa K and Taniguchi N: Possible role of coexpression of CD9 with membrane-anchored heparin-binding EGF-like growth factor and amphiregulin in cultured human keratinocyte growth. J Cell Physiol. 171:291–298. 1997. View Article : Google Scholar : PubMed/NCBI

12 

Berditchevski F and Odintsova E: Characterization of integrintetraspanin adhesion complexes: Role of tetraspanins in integrin signaling. J Cell Biol. 146:477–492. 1999. View Article : Google Scholar : PubMed/NCBI

13 

Baudoux B, Castanares-Zapatero D, Leclercq-Smekens M, Berna N and Poumay Y: The tetraspanin CD9 associates with the integrin alpha6beta4 in cultured human epidermal keratinocytes and is involved in cell motility. Eur J Cell Biol. 79:41–51. 2000. View Article : Google Scholar : PubMed/NCBI

14 

Shi W, Fan H, Shum L and Derynck R: The tetraspanin CD9 associates with transmembrane TGF-alpha and regulates TGF-alpha-induced EGF receptor activation and cell proliferation. J Cell Biol. 148:591–602. 2000. View Article : Google Scholar : PubMed/NCBI

15 

Crnogorac-Jurcevic T, Efthimiou E, Capelli P, Blaveri E, baron A, Terris B, Jones M, Tyson K, Bassi C, Scarpa A, et al: Gene expression profiles of pancreatic cancer and stromal desmoplasia. Oncogene. 20:7437–7446. 2001. View Article : Google Scholar : PubMed/NCBI

16 

Sho M, Adachi M, Taki T, Hashida H, Konishi T, Huang CL, Ikeda N, Nakajima Y, Kanehiro H, Hisanaga M, et al: Transmembrane 4 superfamily as a prognostic factor in pancreatic cancer. Int J Cancer. 79:509–516. 1998. View Article : Google Scholar : PubMed/NCBI

17 

Grønborg M, Kristiansen TZ, Iwahori A, Chang R, Reddy R, Sato N, Molina H, Jensen ON, Hruban RH, Goggins MG, et al: Biomarker discovery from pancreatic cancer secretome using a differential proteomic approach. Mol Cell Proteomics. 5:157–171. 2006. View Article : Google Scholar

18 

Elsässer HP, Lehr U, Agricola B and Kern HF: Establishment and characterisation of two cell lines with different grade of differentiation derived from one primary human pancreatic adenocarcinoma. Virchows Arch B Cell Pathol Incl Mol Pathol. 61:295–306. 1992. View Article : Google Scholar : PubMed/NCBI

19 

Chen G, Kronenberger P, Teugels E, Umelo IA and De Grève J: Targeting the epidermal growth factor receptor in non-small cell lung cancer cells: The effect of combining RNA interference with tyrosine kinase inhibitors or cetuximab. BMC Med. 10:282012. View Article : Google Scholar : PubMed/NCBI

20 

Liang CC, Park AY and Guan JL: In vitro scratch assay: A convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc. 2:329–333. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Brand TM, Iida M, Li C and Wheeler DL: The nuclear epidermal growth factor receptor signaling network and its role in cancer. Discov Med. 12:419–432. 2011.PubMed/NCBI

22 

Sousa LP, Lax I, Shen H, Ferguson SM, De Camilli P and Schlessinger J: Suppression of EGFR endocytosis by dynamin depletion reveals that EGFR signaling occurs primarily at the plasma membrane. Proc Natl Acad Sci USA. 109:4419–4424. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Schroeder B, Weller SG, Chen J, Billadeau D and McNiven MA: A Dyn2-CIN85 complex mediates degradative traffic of the EGFR by regulation of late endosomal budding. EMBO J. 29:3039–3053. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Chen S, Sun Y, Jin Z and Jing X: Functional and biochemical studies of CD9 in fibrosarcoma cell line. Mol Cell Biochem. 350:89–99. 2011. View Article : Google Scholar

25 

Fan J, Zhu GZ and Niles RM: Expression and function of CD9 in melanoma cells. Mol Carcinog. 49:85–93. 2010.

26 

Ono M, Handa K, Withers DA and Hakomori S: Motility inhibition and apoptosis are induced by metastasis-suppressing gene product CD82 and its analogue CD9, with concurrent glycosylation. Cancer Res. 59:2335–2339. 1999.PubMed/NCBI

27 

Copeland BT, Bowman MJ, Boucheix C and Ashman LK: Knockout of the tetraspanin Cd9 in the TRAMP model of de novo prostate cancer increases spontaneous metastases in an organ-specific manner. Int J Cancer. 133:1803–1812. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Ovalle S, Gutiérrez-López MD, Olmo N, Turnay J, Lizarbe MA, Majano P, Molina-Jiménez F, López-Cabrera M, Yáñez-Mó M, Sánchez-Madrid F, et al: The tetraspanin CD9 inhibits the proliferation and tumorigenicity of human colon carcinoma cells. Int J Cancer. 121:2140–2152. 2007. View Article : Google Scholar : PubMed/NCBI

29 

Zheng R, Yano S, Zhang H, Nakataki E, Tachibana I, Kawase I, Hayashi S and Sone S: CD9 overexpression suppressed the liver metastasis and malignant ascites via inhibition of proliferation and motility of small-cell lung cancer cells in NK cell-depleted SCID mice. Oncol Res. 15:365–372. 2005.

30 

Herr MJ, Longhurst CM, Baker B, Homayouni R, Speich HE, Kotha J and Jennings LK: Tetraspanin CD9 modulates human lymphoma cellular proliferation via histone deacetylase activity. Biochem Biophys Res Commun. 447:616–620. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Zöller M: Tetraspanins: Push and pull in suppressing and promoting metastasis. Nat Rev Cancer. 9:40–55. 2009. View Article : Google Scholar

32 

Troiani T, Martinelli E, Capasso A, Morgillo F, Orditura M, De Vita F and Ciardiello F: Targeting EGFR in pancreatic cancer treatment. Curr Drug Targets. 13:802–810. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Nankivell P, Williams H, McConkey C, Webster K, High A, MacLennan K, Senguven B, Rabbitts P and Mehanna H: Tetraspanins CD9 and CD151, epidermal growth factor receptor and cyclooxygenase-2 expression predict malignant progression in oral epithelial dysplasia. Br J Cancer. 109:2864–2874. 2013. View Article : Google Scholar : PubMed/NCBI

34 

Murayama Y, Shinomura Y, Oritani K, Miyagawa J, Yoshida H, Nishida M, Katsube F, Shiraga M, Miyazaki T, Nakamoto T, et al: The tetraspanin CD9 modulates epidermal growth factor receptor signaling in cancer cells. J Cell Physiol. 216:135–143. 2008. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Tang M, Yin G, Wang F, Liu H, Zhou S, Ni J, Chen C, Zhou Y and Zhao Y: Downregulation of CD9 promotes pancreatic cancer growth and metastasis through upregulation of epidermal growth factor on the cell surface. Oncol Rep 34: 350-358, 2015.
APA
Tang, M., Yin, G., Wang, F., Liu, H., Zhou, S., Ni, J. ... Zhao, Y. (2015). Downregulation of CD9 promotes pancreatic cancer growth and metastasis through upregulation of epidermal growth factor on the cell surface. Oncology Reports, 34, 350-358. https://doi.org/10.3892/or.2015.3960
MLA
Tang, M., Yin, G., Wang, F., Liu, H., Zhou, S., Ni, J., Chen, C., Zhou, Y., Zhao, Y."Downregulation of CD9 promotes pancreatic cancer growth and metastasis through upregulation of epidermal growth factor on the cell surface". Oncology Reports 34.1 (2015): 350-358.
Chicago
Tang, M., Yin, G., Wang, F., Liu, H., Zhou, S., Ni, J., Chen, C., Zhou, Y., Zhao, Y."Downregulation of CD9 promotes pancreatic cancer growth and metastasis through upregulation of epidermal growth factor on the cell surface". Oncology Reports 34, no. 1 (2015): 350-358. https://doi.org/10.3892/or.2015.3960
Copy and paste a formatted citation
x
Spandidos Publications style
Tang M, Yin G, Wang F, Liu H, Zhou S, Ni J, Chen C, Zhou Y and Zhao Y: Downregulation of CD9 promotes pancreatic cancer growth and metastasis through upregulation of epidermal growth factor on the cell surface. Oncol Rep 34: 350-358, 2015.
APA
Tang, M., Yin, G., Wang, F., Liu, H., Zhou, S., Ni, J. ... Zhao, Y. (2015). Downregulation of CD9 promotes pancreatic cancer growth and metastasis through upregulation of epidermal growth factor on the cell surface. Oncology Reports, 34, 350-358. https://doi.org/10.3892/or.2015.3960
MLA
Tang, M., Yin, G., Wang, F., Liu, H., Zhou, S., Ni, J., Chen, C., Zhou, Y., Zhao, Y."Downregulation of CD9 promotes pancreatic cancer growth and metastasis through upregulation of epidermal growth factor on the cell surface". Oncology Reports 34.1 (2015): 350-358.
Chicago
Tang, M., Yin, G., Wang, F., Liu, H., Zhou, S., Ni, J., Chen, C., Zhou, Y., Zhao, Y."Downregulation of CD9 promotes pancreatic cancer growth and metastasis through upregulation of epidermal growth factor on the cell surface". Oncology Reports 34, no. 1 (2015): 350-358. https://doi.org/10.3892/or.2015.3960
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