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Article

Netrin-4 overexpression suppresses primary and metastatic colorectal tumor progression

  • Authors:
    • Clarisse Eveno
    • Jean-Olivier Contreres
    • Patricia Hainaud
    • Judith Nemeth
    • Evelyne Dupuy
    • Marc Pocard
  • View Affiliations / Copyright

    Affiliations: INSERM U965 Angiogenesis and Translational Research, Lariboisière Hospital, AP-HP, 75010 Paris, France, Department of Pathology, Paris Diderot, Paris 7 University, Lariboisière Hospital, AP-HP, 75010 Paris, France
  • Pages: 73-78
    |
    Published online on: October 23, 2012
       https://doi.org/10.3892/or.2012.2104
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Abstract

Tumor angiogenesis is closely associated with clinical staging and has been proposed to correlate with clinical response in terms of subsequent metastases following primary resection. Netrin-4 (NT-4) regulates angiogenic responses. Therefore, we sought to examine the effects of NT-4 on the primary tumor growth of colon cancer cells, liver and lung metastases of colon cancer cells, and responses following primary tumor resection. We used 3 different mouse models of orthotopic primary tumor and liver and lung metastases, comparing 2 human colon cancer cells lines: wild-type (low expression of NT-4) and NT-4 (overexpression of NT-4) LS174 cells. NT-4 overexpression inhibited the primary tumor growth of colorectal LS174 xenografts in nude mice (144.3±12.9 vs. 62.4±4.5 mm3; p<0.0001) as well as its related local and systemic recurrence (38 vs. 0%; p<0.01). NT-4 overexpression also markedly decreased colorectal cancer progression in terms of tumor number and volume of liver metastases in the NT-4 group of the orthotopic liver metastasis model (25 vs. 90% and 4±1 vs. 709±190 mm3, p<0.001 and p<0.05). Collectively, our findings indicate that NT-4 overexpression decreases colorectal lung metastasis and its associated lymph node involvement. NT-4 overexpression decreases tumor recurrence and metastasis after surgical resection, likely via an anti-angiogenic effect. These observations suggest that NT-4 may hold therapeutic potential in the treatment of colorectal cancer growth and major metastatic sites.
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Copy and paste a formatted citation
Spandidos Publications style
Eveno C, Contreres J, Hainaud P, Nemeth J, Dupuy E and Pocard M: Netrin-4 overexpression suppresses primary and metastatic colorectal tumor progression. Oncol Rep 29: 73-78, 2013.
APA
Eveno, C., Contreres, J., Hainaud, P., Nemeth, J., Dupuy, E., & Pocard, M. (2013). Netrin-4 overexpression suppresses primary and metastatic colorectal tumor progression. Oncology Reports, 29, 73-78. https://doi.org/10.3892/or.2012.2104
MLA
Eveno, C., Contreres, J., Hainaud, P., Nemeth, J., Dupuy, E., Pocard, M."Netrin-4 overexpression suppresses primary and metastatic colorectal tumor progression". Oncology Reports 29.1 (2013): 73-78.
Chicago
Eveno, C., Contreres, J., Hainaud, P., Nemeth, J., Dupuy, E., Pocard, M."Netrin-4 overexpression suppresses primary and metastatic colorectal tumor progression". Oncology Reports 29, no. 1 (2013): 73-78. https://doi.org/10.3892/or.2012.2104
Copy and paste a formatted citation
x
Spandidos Publications style
Eveno C, Contreres J, Hainaud P, Nemeth J, Dupuy E and Pocard M: Netrin-4 overexpression suppresses primary and metastatic colorectal tumor progression. Oncol Rep 29: 73-78, 2013.
APA
Eveno, C., Contreres, J., Hainaud, P., Nemeth, J., Dupuy, E., & Pocard, M. (2013). Netrin-4 overexpression suppresses primary and metastatic colorectal tumor progression. Oncology Reports, 29, 73-78. https://doi.org/10.3892/or.2012.2104
MLA
Eveno, C., Contreres, J., Hainaud, P., Nemeth, J., Dupuy, E., Pocard, M."Netrin-4 overexpression suppresses primary and metastatic colorectal tumor progression". Oncology Reports 29.1 (2013): 73-78.
Chicago
Eveno, C., Contreres, J., Hainaud, P., Nemeth, J., Dupuy, E., Pocard, M."Netrin-4 overexpression suppresses primary and metastatic colorectal tumor progression". Oncology Reports 29, no. 1 (2013): 73-78. https://doi.org/10.3892/or.2012.2104
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