title: Inhibition of breast cancer growth and metastasis by a biomimetic peptide.
abstract: Metastasis is the main cause of mortality in cancer patients. Though there are many anti-cancer drugs targeting primary tumor growth, anti-metastatic agents are rarely developed. Angiogenesis and lymphangiogenesis are crucial for cancer progression, particularly, lymphangiogenesis is pivotal for metastasis in breast cancer. Here we report that a novel collagen IV derived biomimetic peptide inhibits breast cancer growth and metastasis by blocking angiogenesis and lymphangiogenesis. The peptide inhibits blood and lymphatic endothelial cell viability, migration, adhesion, and tube formation by targeting IGF1R and Met signals. The peptide blocks MDA-MB-231 tumor growth by inhibiting tumor angiogenesis in vivo. Moreover, the peptide inhibits lymphangiogenesis in primary tumors. MDA-MB-231 tumor conditioned media (TCM) was employed to accelerate spontaneous metastasis in tumor xenografts, and the anti-metastatic activity of the peptide was tested in this model. The peptide prevents metastasis to the lungs and lymph nodes by inhibiting TCM-induced lymphangiogenesis and angiogenesis in the pre-metastatic organs. In summary, a novel biomimetic peptide inhibits breast cancer growth and metastasis by blocking angiogenesis and lymphangiogenesis in the pre-metastatic organs as well as primary tumors.
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States.
authors.forename: Esak
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States.
authors.forename: Seung Jae
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States.
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Koskimaki
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States.
authors.forename: Zheyi
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States.
authors.forename: Niranjan B
authors.initials: NB
authors.lastname: Pandey
authors.affiliation: 1] Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States [2] Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States.
authors.forename: Aleksander S
authors.initials: AS
authors.lastname: Popel
mesh_terms: D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D024141:Collagen Type IV / Q000737:chemistry; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D042583:Lymphangiogenesis / Q000187:drug effects; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D024141:Collagen Type IV; D017077:Culture Media, Conditioned; D010455:Peptides