Publications

Authors:

Carbone, C.; Moccia, T.; Zhu, C.; Paradiso, G.; Budillon, A.; Chiao, P. J.; Abbruzzese, J. L.; Melisi, Davide

Title:

Anti-VEGF treatment-resistant pancreatic cancers secrete proinflammatory factors that contribute to malignant progression by inducing an EMT cell phenotype.

Year:

2011

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Referee:

No

Name of journal:

Clinical Cancer Research

ISSN of journal:

1078-0432

N° Volume:

17

Page numbers:

5822-5832

Keyword:

anti-VEGF resistance; proinflammatory factors; EMT; pancreatic cancer

Short description of contents:

The resistance of tumors to antiangiogenic therapies is becoming increasingly relevant. There are currently no validated predictive biomarkers for selecting which cancer patients will benefit from antiangiogenic therapy. Also lacking are resistance biomarkers that can identify which escape pathways should be targeted after tumors develop resistance to VEGF treatment. Recent studies showed that anti-VEGF treatment can make tumor cells more aggressive and metastatic. However, the mechanisms and mediators of this are unidentified. Therefore, we aimed this study at directly identifying the tumor cell-initiated mechanisms responsible for the resistance of pancreatic cancer to anti-VEGF treatment.We established and validated two murine models of human pancreatic cancer resistant to the VEGF-specific antibody bevacizumab in vivo. We used a genome-wide analysis to directly identify which tumor-secreted factors were overexpressed by pancreatic cancer cells that were resistant to anti-VEGF treatment.Rather than direct proangiogenic factors, we identified several proinflammatory factors that were expressed at higher levels in cells resistant to anti-VEGF treatment than in treatment-sensitive control cells. These proinflammatory factors acted in a paracrine manner to stimulate the recruitment of CD11b(+) proangiogenic myeloid cells. Also, we found that secreted factors overexpressed by anti-VEGF treatment-resistant pancreatic cancer cells acted in an autocrine manner to induce epithelial-to-mesenchymal transition (EMT) and were thus responsible for increased aggressiveness of bevacizumab-resistant pancreatic tumors.Our results identified proinflammatory factors and EMT markers as potential biomarkers for selecting patients with pancreatic cancer for antiangiogenic therapy.

Web page:

http://dx.doi.org/10.1158/1078-0432.CCR-11-1185

Product ID:

65794

Handle IRIS:

11562/388919

Deposited On:

February 16, 2012

Last Modified:

November 27, 2022

Bibliographic citation:

Carbone, C.; Moccia, T.; Zhu, C.; Paradiso, G.; Budillon, A.; Chiao, P. J.; Abbruzzese, J. L.; Melisi, Davide, Anti-VEGF treatment-resistant pancreatic cancers secrete proinflammatory factors that contribute to malignant progression by inducing an EMT cell phenotype. «Clinical Cancer Research» , vol. 17 , 2011 , pp. 5822-5832

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