title: Targeting of crosstalk between tumor and tumor microenvironment by β-D mannuronic acid (M2000) in murine breast cancer model.
abstract: Metastasis is the main cause of death in breast cancer patients. Inflammatory processes following crosstalk between tumor cells and tumor microenvironment play an important role in progression and metastasis of cancer. Hence, targeting of these interactions may represent a novel promising strategy for breast cancer therapy. So, we investigated the effects of β-D mannuronic acid (BDM), a new antiinflammatory agent, on 4T1 breast cancer cell line both in vitro and in vivo. Proliferation assays revealed low-cytotoxic effect of BDM on 4T1 cells. However, BDM reduced activity of MMP-2, MMP-9 and significantly decreased the adhesion of 4T1 cells to extracellular matrix (ECM) in a dose-dependent manner. The in vivo results demonstrated that BDM strongly inhibits tumor growth and increases lifespan as compared with control mice. The decrease in tumor mass was associated with decreased metastasis, recruitment, and frequency of inflammatory cells in tumor tissue. Our preclinical findings demonstrated that BDM therapy not only prevents formation of chronic inflammatory response but also inhibits crosstalk between tumor cells and their microenvironment, which is associated with reduction of tumor growth and metastasis arrest. Our data imply the use of BDM therapy in future clinical trials to open a new horizon for breast cancer therapy.
authors.affiliation: Cancer Research Center and Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Hosseini
authors.affiliation: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Hadi
authors.initials: H
authors.lastname: Hassannia
authors.affiliation: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Mahdian-Shakib
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.|Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Farhad
authors.initials: F
authors.lastname: Jadidi-Niaragh
authors.affiliation: Department of Molecular Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
authors.forename: Seyed Ehsan
authors.initials: SE
authors.lastname: Enderami
authors.affiliation: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.|Shiraz institute for cancer research, Shiraz, University of Medical Sciences, Shiraz, Iran.
authors.forename: Mohammadjavad
authors.initials: M
authors.lastname: Fattahi
authors.affiliation: Department of Veterinary Medicine, Islamic Azad University, Abhar, Abhar branch, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Anissian
authors.affiliation: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Mirshafiey
authors.affiliation: Cancer Research Center and Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran.|Department of Oncology-Pathology, Immune and Gene Therapy Laboratory, Cancer Centre Karolinska, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Parviz
authors.identifier: 0000-0001-6544-4209
authors.initials: P
authors.lastname: Kokhaei
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006603:Hexuronic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D009362:Neoplasm Metastasis; D047368:Tumor Burden / Q000187:drug effects; D059016:Tumor Microenvironment / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000893:Anti-Inflammatory Agents; D006603:Hexuronic Acids; C008324:mannuronic acid; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: M2000; breast cancer; metastasis; β-D-mannuronic acid