Pubblicazioni

Anti-VEGF treatment-resistant pancreatic cancers secrete proinflammatory factors that contribute to malignant progression by inducing an EMT cell phenotype.  (2011)

Autori:
C. Carbone;T. Moccia;C. Zhu;G. Paradiso;A. Budillon;P. J. Chiao;J. L. Abbruzzese;D. Melisi
Titolo:
Anti-VEGF treatment-resistant pancreatic cancers secrete proinflammatory factors that contribute to malignant progression by inducing an EMT cell phenotype.
Anno:
2011
Tipologia prodotto:
Articolo in Rivista
Tipologia ANVUR:
Articolo su rivista
Lingua:
Inglese
Formato:
A Stampa
Referee:
No
Nome rivista:
Clinical Cancer Research
ISSN Rivista:
1078-0432
N° Volume:
17
Intervallo pagine:
5822-5832
Codice PMID:
21737511
Parole chiave:
anti-VEGF resistance, proinflammatory factors, EMT, pancreatic cancer
Breve descrizione dei contenuti:
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.
Pagina Web:
http://dx.doi.org/10.1158/1078-0432.CCR-11-1185
Id prodotto:
65794
Handle IRIS:
11562/388919
depositato il:
16 febbraio 2012
ultima modifica:
2 novembre 2016
Citazione bibliografica:
C. Carbone;T. Moccia;C. Zhu;G. Paradiso;A. Budillon;P. J. Chiao;J. L. Abbruzzese;D. Melisi, Anti-VEGF treatment-resistant pancreatic cancers secrete proinflammatory factors that contribute to malignant progression by inducing an EMT cell phenotype. «Clinical Cancer Research» , vol. 172011pp. 5822-5832

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo IRIS

Progetti Collegati
Titolo Dipartimento Responsabili
Mechanisms of resistance to chemoterapeutic and antiangiogenic drugs as novel targets for pancreatic cancer therapy Dipartimento Medicina Davide Melisi
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