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

被引:14
作者
Rosca, Elena V. [1 ]
Koskimaki, Jacob E. [1 ]
Pandey, Niranjan B. [1 ]
Wolff, Antonio C. [2 ,3 ]
Popel, Aleksander S. [1 ,2 ,3 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Sch Med, Baltimore, MD 21205 USA
基金
美国国家卫生研究院;
关键词
angiogenesis; cancer therapy; drug development; integrins; triple-negative; xenograft; NONNATURAL AMINO-ACIDS; TUMOR-GROWTH; ENDOTHELIAL-CELLS; PHASE-I; INHIBITORS; BEVACIZUMAB; PACLITAXEL; PROTEINS; DESIGN; THERAPEUTICS;
D O I
10.4161/cbt.12.9.17677
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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-alpha-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.
引用
收藏
页码:808 / 817
页数:10
相关论文
共 37 条
  • [1] The endothelial cell tube formation assay on basement membrane turns 20: state of the science and the art
    Arnaoutova, Irina
    George, Jay
    Kleinman, Hynda K.
    Benton, Gabriel
    [J]. ANGIOGENESIS, 2009, 12 (03) : 267 - 274
  • [2] Cilengitide (EMD 121974, NSC 707544) in asymptomatic metastatic castration resistant prostate cancer patients: a randomized phase II trial by the prostate cancer clinical trials consortium
    Bradley, Deborah A.
    Daignault, Stephanie
    Ryan, Charles J.
    DiPaola, Robert S.
    Smith, David C.
    Small, Eric
    Gross, Mitchell E.
    Stein, Mark N.
    Chen, Alice
    Hussain, Maha
    [J]. INVESTIGATIONAL NEW DRUGS, 2011, 29 (06) : 1432 - 1440
  • [3] Angiogenesis in life, disease and medicine
    Carmeliet, P
    [J]. NATURE, 2005, 438 (7070) : 932 - 936
  • [4] Angiogenesis in cancer and other diseases
    Carmeliet, P
    Jain, RK
    [J]. NATURE, 2000, 407 (6801) : 249 - 257
  • [5] The clinical potential of antiangiogenic fragments of extracellular matrix proteins
    Clamp, AR
    Jayson, GC
    [J]. BRITISH JOURNAL OF CANCER, 2005, 93 (09) : 967 - 972
  • [6] Drevs J, 2010, ANTICANCER RES, V30, P2335
  • [7] Two functional epitopes of pigment epithelial-derived factor block angiogenesis and induce differentiation in prostate cancer
    Filleur, S
    Volz, K
    Nelius, T
    Mirochnik, Y
    Huang, HH
    Zaichuk, TA
    Aymerich, MS
    Becerra, SP
    Yap, R
    Veliceasa, D
    Shroff, EH
    Volpert, OV
    [J]. CANCER RESEARCH, 2005, 65 (12) : 5144 - 5152
  • [8] Angiogenesis
    Folkman, J
    [J]. ANNUAL REVIEW OF MEDICINE, 2006, 57 : 1 - 18
  • [9] Replacement of Ala by Aib improves structuration and biological stability in thymine-based α-nucleopeptides
    Geotti-Bianchini, Piero
    Moretto, Alessandro
    Peggion, Cristina
    Beyrath, Julien
    Bianco, Alberto
    Formaggio, Fernando
    [J]. ORGANIC & BIOMOLECULAR CHEMISTRY, 2010, 8 (06) : 1315 - 1321
  • [10] In vitro assays of angiogenesis for assessment of angiogenic and anti-angiogenic agents
    Goodwin, Anne M.
    [J]. MICROVASCULAR RESEARCH, 2007, 74 (2-3) : 172 - 183