title: Proteomic analysis of cancer and mesothelial cells reveals an increase in Mucin 5AC during ovarian cancer and peritoneal interaction.
abstract: Ovarian cancer is a highly metastatic disease that is often characterized by widespread abdominal dissemination. A hallmark of ovarian cancer progression is the attachment of malignant cells to the mesothelium and the formation of invasive peritoneal implants. Therefore, delineating factors involved in cancer-peritoneal cell interaction is critical to improving patient survival, as it may lead to the discovery of novel therapeutic targets. As such, we aimed to identify proteins that participate in this interaction by comparing the secreted proteome of a co-culture model containing ovarian cancer (OVCAR-5) and mesothelial cells (LP-9), to their respective monoculture secretomes. In total, 49 proteins were differentially secreted during cancer and mesothelial cell contact. Relative mRNA expression of candidates was performed, which revealed a significant increase in MUC5AC gene expression in cancer cells cultured in three different co-culture models (OVCAR-5 and LP-9; BG-1 and LP-9; OV-90 and LP-9). An increased expression was also observed in LP-9 cells that were co-cultured with OVCAR-5 and OV-90 cancer cells. Further immunocytochemistry analysis also confirmed increased expression of MUC5AC in ovarian cancer and peritoneal co-cultures. Overall, our analysis uncovers novel molecular markers of peritoneal metastasis, which may have potential roles in regulating the progression of the disease.
  
  
  CONCLUSIONS
  In this study, our objective was to focus on identifying novel mediators of ovarian cancer and peritoneal interaction using a mass spectrometry-based approach. Our analysis resulted in the discovery of both previously known and novel factors involved this interaction, and as such, these newly discovered proteins might have potential roles in cancer progression, such as invasion and adhesion. We believe that these findings add to our current knowledge and understanding of ovarian cancer progression, and will aid researchers in their future attempts in finding new targets of the disease.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Natasha
authors.initials: N
authors.lastname: Musrap
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: George S
authors.initials: GS
authors.lastname: Karagiannis
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Punit
authors.initials: P
authors.lastname: Saraon
authors.affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Ihor
authors.initials: I
authors.lastname: Batruch
authors.affiliation: Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Smith
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, Canada. Electronic address: ediamandis@mtsinai.on.ca.
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
mesh_terms: D045744:Cell Line, Tumor; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D055271:Mucin 5AC / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D009363:Neoplasm Proteins / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000737:chemistry / Q000556:secondary; D040901:Proteomics / Q000379:methods*
chemical_list: D017077:Culture Media, Conditioned; D055271:Mucin 5AC; D009363:Neoplasm Proteins
keywords: Co-culture; Metastasis; Mucin 5AC; Ovarian cancer; Peritoneum; Proteomics