Cisplatin-Induced Changes in Proteomic Profiles of Ovarian Cancer Cell and Fibroblast Secretomes

ABSTRACT: Exogenous signals from drug-stressed cancer cells promote acquisition of a more aggressive phenotype of neighboring tumor cells. To identify extracellular signaling molecules that potentially contribute to the development of therapy resistance, we examined how cancer cell secretome changes in response to chemotherapy. We performed LC-MS/MS analysis of conditioned media (CM) from ovarian cancer cells SKOV3 before and 48 hours after cisplatin treatment. We identified 1,820 and 784 proteins in secretomes of cancer cells treated or untreated with cisplatin, respectively. Functional annotation of proteins which secretion increased after cisplatin showed that these proteins were mainly associated with cluster of spliceosome. To investigate whether secretion of spliceosomal proteins during induction of apoptosis is a specific property of tumor cells, we compared proteomes of CM from primary culture of normal human skin fibroblasts before and 48 hours after exposure to cisplatin (IC50). A LC-MS/MS analysis revealed that most of the proteins in the CM of fibroblasts and cancer cells under normal conditions overlap, while the secretomes after therapy demonstrate much more pronounced differences. GO and KEGG enrichment analysis revealed higher abundance of cell adhesion and extracellular matrix proteins in CM of fibroblasts before chemotherapy; while lysosomal proteins and growth factors, associated with wound healing were increased after cisplatin treatment. Spliceosomal proteins were only slightly present in fibroblast CM and did not show any changes in a response to chemotherapy. We suggest that the acquisition of ovarian cancer chemoresistance might be partially mediated by extracellular spliceosomal components.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: Georgij Arapidi  

LAB HEAD: Georgij Arapidi

PROVIDER: PXD019096 | Pride | 2024-05-29

REPOSITORIES: Pride