alexa Notch Activation Modulates Bevacizumab Activity by CD44 Positive Cancer Stem Cells in Advanced Colon Cancer | OMICS International| Abstract

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  • Research Article   
  • J Mol Biomark Diagn 2017, Vol 8(5): S2-036
  • DOI: 10.4172/2155-9929.S2-036

Notch Activation Modulates Bevacizumab Activity by CD44 Positive Cancer Stem Cells in Advanced Colon Cancer

Negri FV1*#, Bozzetti C1#, Pedrazzi G2, Azzoni C3, Bottarelli L3, Squadrilli A1, Lagrasta C4, Tamagnini I5, Bisagni A5, Ragazzi M5, Madeddu D6, Falco A6, Gervasi A6, Porzio R7, Tomasello G8, Leonardi F1, Ardizzoni A9, Sala R4, Gnetti L10, Crafa P10, Quaini F6 and Cascinu S11
1Medical Oncology Unit, University Hospital of Parma, , Italy
2Department of Medicine and Surgery, Unit of Neuroscience, University of Parma, Italy
3Department of Biomedical, Biotechnological and Translational Sciences, Centre for Molecular and Translational Oncology (COMT), Unit of Pathological Anatomy, University Hospital of Parma, , Italy
4Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Italy
5Department of Pathology, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Santa Maria Nuova Hospital, , Italy
6Department of Clinical and Experimental Medicine, University Hospital of Parma, , Italy
7Medical Oncology Unit, Azienda Unità Sanitaria Locale, , Italy
8Medical Oncology Unit, Azienda Istituti Ospitalieri, , Italy
9Medical Oncology Unit, St Orsola-Malpighi University Hospital, , Italy
10Pathologic Anatomy Unit, University Hospital of Parma, , Italy
11Department of Medical and Surgical Sciences for Children and Adults, Division of Medical Oncology, University Hospital of Modena and Reggio Emilia, , Italy
#Contributed equally to this work
*Corresponding Author : Negri FV, Medical Oncology Unit, University Hospital, Via Gramsci 14, 43126 Parma, Italy, Tel: 0039 0521702676, Fax: 0039 0521995448, Email: [email protected]

Received Date: Jul 14, 2017 / Accepted Date: Sep 12, 2017 / Published Date: Sep 14, 2017


Background: Notch pathway is involved in regulating colon cancer stem cells (CSCs), which play an important role in angiogenesis and resistance to conventional therapies. CD44 and CD133 are transmembrane glycoproteins reported as putative markers for isolating CSCs. High expression of Notch Intracellular Cleaved Domain (NICD) has been associated with resistance to anti-vascular endothelial growth factor therapy. Based on these reports, we evaluated NICD, CD44 and CD133 expression in a series of consecutive metastatic colon cancer patients treated with bevacizumab-based chemotherapy within first-line clinical trials.

Methods: Histological samples obtained from 45 primary adenocarcinomas were tested by immunohistochemistry for NICD, CD44 and CD133. A scoring system based on staining intensity and percentage of stained cells was used. Vessels density was measured in hot-spot areas by CD31 antibody.

Results: CD44 levels were higher in high NICD cases than in low NICD cases (63% vs. 16%, respectively, p=0.014). High NICD and CD44 levels predicted shorter progression-free (p<0.001) and overall survival (p=0.012). No significant association was found between CD133 or CD31 and NICD or CD44 expression.

Conclusion: Our data suggest that colon cancer patient with high NICD and CD44 levels have a reduced likelihood of response to bevacizumab-based therapy.

Keywords: Colorectal cancer; bevacizumab; Notch; CD44; Stem cells; Angiogenesis

Citation: Negri FV, Bozzetti C, Pedrazzi G, Azzoni C, Bottarelli L, et al. (2017) Notch Activation Modulates Bevacizumab Activity by CD44 Positive Cancer Stem Cells in Advanced Colon Cancer. J Mol Biomark Diagn S2: 036. Doi: 10.4172/2155-9929.S2-036

Copyright: ©2017 Negri FV, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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