Development of a biomimetic peptide derived from collagen IV with anti-angiogenic activity in breast cancer.

Abstract:

:Breast cancer is one of the most commonly diagnosed malignancies in women. Despite the remarkable success of mammography screening and use of adjuvant systemic therapy, it is estimated that approximately 200,000 new diagnoses will be made this year and 40,000 deaths will occur due to this disease (American Cancer Society). Angiogenesis, the growth of vessels from pre-existing microvasculature, is an essential component of tumor progression and has emerged as a therapeutic modality for anti-angiogenic therapies in cancer. Here we report in vitro and in vivo findings with a 20 amino acid peptide belonging to the collagen IV family, modified to facilitate possible translation to clinical applications. The two cysteines in its natural peptide progenitor were replaced by L-α-amino-n-butyric acid, a non-natural amino acid. The modified peptide was tested in vitro using endothelial cells and in vivo using mouse orthotopic breast cancer xenograft model with MDA-MB-231 human breast cancer cells. This modified peptide demonstrated no significant changes in activity from the parent peptide; however, because it lacks cysteines, it is more suitable for clinical translation. We also investigated its efficacy in combination with a commonly used chemotherapeutic agent paclitaxel; the inhibition of tumor growth by the peptide was similar to that of paclitaxel alone, but the combination did not exhibit any additional inhibition. We have performed further characterization of the mechanism of action (MOA) for this peptide to identify its target receptors, enhancing its translation potential as an anti-angiogenic, non-vascular endothelial growth factor (VEGF) targeting agent for therapy in breast cancer.

journal_name

Cancer Biol Ther

journal_title

Cancer biology & therapy

authors

Rosca EV,Koskimaki JE,Pandey NB,Wolff AC,Popel AS

doi

10.4161/cbt.12.9.17677

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

808-17

issue

9

eissn

1538-4047

issn

1555-8576

pii

17677

journal_volume

12

pub_type

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