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Comparative Proteomic Analysis of the Mitochondria of Menstrual Stem Cells and Ovarian Cancer Cells

ABSTRACT: Mitochondria transplantation is a hot spot in cell-free therapy. Menstrual stem cells (MenSCs) are potential donor cells to provide foreign mitochondria. This study aims to investigate the possible effects of MenSC-derived mitochondria on ovarian cancer from the perspective of protein expression profiling. MenSCs were harvested from menstrual blood. The mitochondria were isolated from MenSCs and ovarian cancer cell line-SKOV3. A label-free proteomics and analysis were performed by comparing the protein expression in the mitochondria of MenSCs and SKOV3 cells. The differentially expressed proteins with fold change higher than 2 were analyzed by Gene Ontology, KEGG pathway and protein domain enrichment analysis, protein interaction networks and PRM analysis. In total, 592 proteins which were up-expressed in the mitochondria of MenSCs were taken to be analyzed. Functional enrichment analysis revealed these proteins were enriched in metabolism-related pathway entries including oxidative phosphorylation (OXPHOS) pathway. Parallel Reaction Monitoring (PRM) analysis confirmed that 4 out of 6 candidate proteins on OXPHOS pathway afforded similar trends. The protein domain enrichment analysis showed that the domains such as thioredoxin domain were significantly enriched. Based on these findings, we believed that the mitochondria from MenSCs might work to enhance the progression of ovarian cancer, which was probably mediated by the enrichment of OXPHOS-related metabolic pathways.

INSTRUMENT(S): MaxQuant

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Adult Stem Cell

SUBMITTER: wen zhong

LAB HEAD: Xiuhui Chen

PROVIDER: PXD036148 | Pride | 2022-10-12

REPOSITORIES: Pride

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Project description:Endometriosis is associated with aberrant gene expression in the eutopic endometrium of women with disease. To determine if the development of endometriotic lesions directly impacts eutopic endometrial gene expression, we sequentially analyzed the eutopic endometrium across the time course of disease progression in a baboon model of induced disease. Endometriosis was induced in baboons by intraperitoneal inoculation of autologous menstrual endometrium. Eutopic endometria were collected at 9-11 days postovulation) in five time points: 1, 3, 6-7, 10-12, and 15-16 months after disease induction and compared with tissue from disease-free baboons. We used microarrays to identify differentially expressed genes between time points. Sequential analysis of the same animals during disease progression demonstrated an early disease insult and a transitory dominance of an estrogenic phenotype. However, as the disease progressed, a progesterone-resistant phenotype became evident. Endometriosis was experimentally induced in Papio anubis female baboons (n = 4) by intraperitoneal inoculation with menstrual endometrium on two consecutive menstrual cycles. Baboons with spontaneous endometriosis (n = 2) were also included in this study with an unknown duration of disease. Control endometrium was similarly harvested from animals (n = 4) with no previous surgeries and with no visible disease. The progression of disease was monitored in each animal by consecutive laparoscopies and video recording at 1 (n = 2), 3 (n = 4), 6-7 (n = 4), 10-12, (n = 4), and 15-16 (n = 3) months after inoculation during a window of 9-11 days postovulation. Eutopic endometrial tissues were harvested and were snap frozen in liquid nitrogen for RNA extraction. Additionally, menstrual endometrium was harvested on Days 1-2 of menses using a Unimar Pipelle (Cooper Surgical Inc., Shelton, CT) immediately prior to laparoscopy. Blood samples were collected daily from days 7 through 16 postmenstruation of menstrual cycles.

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Comparative Proteomic Analysis of the Mitochondria of Menstrual Stem Cells and Ovarian Cancer Cells

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