title: Migrastatin analogues inhibit canine mammary cancer cell migration and invasion.
abstract: BACKGROUND
  Cancer spread to other organs is the main cause of death of oncological patients. Migration of cancer cells from a primary tumour is the crucial step in the complex process of metastasis, therefore blocking this process is currently the main treatment strategy. Metastasis inhibitors derived from natural products, such as, migrastatin, are very promising anticancer agents. Thus, the aim of our study was to investigate the effect of six migrastatin analogues (MGSTA-1 to 6) on migration and invasion of canine mammary adenocarcinoma cell lines isolated from primary tumours and their metastases to the lungs. Canine mammary tumours constitute a valuable tool for studying multiple aspect of human cancer.
  
  
  RESULTS
  OUR RESULTS SHOWED THAT TWO OF SIX FULLY SYNTHETIC ANALOGUES OF MIGRASTATIN: MGSTA-5 and MGSTA-6 were potent inhibitors of canine mammary cancer cells migration and invasion. These data were obtained using the wound healing test, as well as trans-well migration and invasion assays. Furthermore, the treatment of cancer cells with the most effective compound (MGSTA-6) disturbed binding between filamentous F-actin and fascin1. Confocal microscopy analyses revealed that treatment with MGSTA-6 increased the presence of unbound fascin1 and reduced co-localization of F-actin and fascin1 in canine cancer cells. Most likely, actin filaments were not cross-linked by fascin1 and did not generate the typical filopodial architecture of actin filaments in response to the activity of MGSTA-6. Thus, administration of MGSTA-6 results in decreased formation of filopodia protrusions and stress fibres in canine mammary cancer cells, causing inhibition of cancer migration and invasion.
  
  
  CONCLUSIONS
  Two synthetic migrastatin analogues (MGSTA-5 and MGSTA-6) were shown to be promising compounds for inhibition of cancer metastasis. They may have beneficial therapeutic effects in cancer therapy in dogs, especially in combination with other anticancer drugs. However, further in vivo studies are required to verify this hypothesis.
authors.affiliation: Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland ; Department of Animal Environment Biology, Faculty of Animal Sciences, Warsaw University of Life Sciences, Warsaw, Poland.
authors.forename: Kinga
authors.initials: K
authors.lastname: Majchrzak
authors.forename: Daniele
authors.initials: D
authors.lastname: Lo Re
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Gajewska
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Bulkowska
authors.forename: Agata
authors.initials: A
authors.lastname: Homa
authors.forename: Karol
authors.initials: K
authors.lastname: Pawłowski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Motyl
authors.forename: Paul V
authors.initials: PV
authors.lastname: Murphy
authors.forename: Magdalena
authors.initials: M
authors.lastname: Król
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen; D003599:Cytoskeleton / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006801:Humans; D007797:Laminin; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015674:Mammary Neoplasms, Animal / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008840:Microfilament Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D008956:Models, Chemical; D015394:Molecular Structure; D009361:Neoplasm Invasiveness; D010881:Piperidones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011509:Proteoglycans
chemical_list: D000199:Actins; D004338:Drug Combinations; D007797:Laminin; D018942:Macrolides; D008840:Microfilament Proteins; D010881:Piperidones; D011509:Proteoglycans; C418199:migrastatin; C059485:matrigel; D003094:Collagen