title: The impact of different extracellular matrices on melatonin effect in proliferation and stemness properties of ovarian cancer cells.
abstract: OBJECTIVE
  Endogenous melatonin has numerous physiological roles on modulating the function of different organs. Recent studies revealed oncostatic and protective effects of this molecule on tumor development. In this study, we examined the impact of melatonin and key underlying mechanisms on stemness, morphology, invasiveness and viability of SKOV3 ovarian cancer cells in different types of extracellular matrix.
  
  
  METHODS
  Cell viability was evaluated by MTT Assay. Colony-forming assay was performed by seeding 4×103cells on different matrices in six well-plate. The percentage of cancer stem like cells was determined by flow cytometric assay after applying antibodies against stemness markers, CD133 and CD44. Different types of extracellular matrix including fibronectin, gelatin, collagen and matrigel were applied to incubate the cells in the presence of melatonin. Downstream gene expressions including VEGF and E-cadherin were determined by Real-time PCR.
  
  
  RESULTS
  Melatonin (0.1mM) decreased the percentage of viable cells up to 61.79±8.2% (p<0.05). Colony formation assay revealed the significant impact of melatonin in inhibition of colony formation in these cells. The maximum effect was shown in the cells incubated with melatonin on gelatin (p<0.05). Identification of stemness markers showed that applying matrigel caused significant increase in the percentage of cancer stem like cells compared to other types of extracellular matrix (p<0.05). However melatonin slightly diminished the number of stem cell like cells in all incubated matrices. Our results from gene expression assays revealed that melatonin induced a marked increase in E-cadherin along with decrease in VEGF expression levels (p<0.05).
  
  
  CONCLUSIONS
  Our results suggest that interaction between ovarian cancer cells and neighboring matrices determines the subsequent anti invasive activities of melatonin.
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Biochemistry and Clinical Laboratories, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Akbarzadeh
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Rahbarghazi
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Elahe
authors.initials: E
authors.lastname: Nabat
authors.affiliation: Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Movassaghpour
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Daruish
authors.initials: D
authors.lastname: Shanehbandi
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Behnaz
authors.initials: B
authors.lastname: Faramarzian Azimi Maragheh
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Danial
authors.initials: D
authors.lastname: Matluobi
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Balal
authors.initials: B
authors.lastname: Barazvan
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Masoume
authors.initials: M
authors.lastname: Kazemi
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Biochemistry and Clinical Laboratories, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: nsamadi@ualberta.ca.
authors.forename: Nasser
authors.initials: N
authors.lastname: Samadi
authors.affiliation: Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: Nourimd@tbzmed.ac.ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Nouri
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008550:Melatonin
keywords: Cancer stem like cell; Extracellular matrix; Melatonin; Ovarian cancer; Viability