title: Intratumoral NAMI-A treatment triggers metastasis reduction, which correlates to CD44 regulation and tumor infiltrating lymphocyte recruitment.
abstract: Intratumor (i.t.) injection of 35 mg/kg/day NAMI-A for six consecutive days to CBA mice bearing i.m. implants of MCa mammary carcinoma reduces primary tumor growth and particularly lung metastasis formation, causing 60% of animals to be free of macroscopically detectable metastases. The i.t. treatment allows study of the effects of NAMI-A on in vivo tumor cells exposed to millimolar concentrations for a relatively prolonged time. Under these conditions, NAMI-A reduces the number of CD44+ tumor cells and changes tumor cell phenotype to a lower aggressive behavior, as shown by scanning electron microscopy analysis. On primary tumor site, NAMI-A causes unbalance between 2n and aneuploid cells in favor of lymphocytes. Furthermore, in tumor tissue, nitric oxide production is increased and active matrix metalloproteinase 9 is decreased, and these effects are accompanied by a reduced hemoglobin concentration. These data are in agreement with the reduction of tumor invasion and metastasis and suggest the therapeutic usefulness of NAMI-A in neoadjuvant or tumor reduction treatments for preventing metastasis formation. These data further stress the usefulness of intratumor treatments as experimental preclinical model for studying in vivo the mechanism of tumor cell interactions after prolonged exposure to ruthenium-based compounds to be developed for metastasis inhibition.
authors.affiliation: Department of Biomedical Sciences, University of Trieste, via L. Giorgieri 7-9, 34127 Trieste, Italy. pacorsab@univ.trieste.it
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pacor
authors.forename: Sonia
authors.initials: S
authors.lastname: Zorzet
authors.forename: Moreno
authors.initials: M
authors.lastname: Cocchietto
authors.forename: Marina
authors.initials: M
authors.lastname: Bacac
authors.forename: Marta
authors.initials: M
authors.lastname: Vadori
authors.forename: Claudia
authors.initials: C
authors.lastname: Turrin
authors.forename: Barbara
authors.initials: B
authors.lastname: Gava
authors.forename: Anna
authors.initials: A
authors.lastname: Castellarin
authors.forename: Gianni
authors.initials: G
authors.lastname: Sava
mesh_terms: D000818:Animals; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D005260:Female; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000378:metabolism*; D015552:Injections, Intralesional; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects* / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D009942:Organometallic Compounds / Q000008:administration & dosage*; D012428:Ruthenium / Q000378:metabolism; D017975:Ruthenium Compounds
chemical_list: D018960:Hyaluronan Receptors; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); D012428:Ruthenium; D004121:Dimethyl Sulfoxide