Mesothelial-to-Mesenchymal Transition and Exosomes in Peritoneal Metastasis of Ovarian Cancer
Most patients with ovarian cancer (OvCA) present peritoneal disseminated disease at the time of diagnosis. During peritoneal metastasis, cancer cells detach from the primary tumor and disseminate through the intraperitoneal fluid. The peritoneal mesothelial cell (PMC) monolayer that lines the abdomi...
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| Veröffentlicht in: | International journal of molecular sciences 2021-10, Vol.22 (21), p.11496 |
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| description | Most patients with ovarian cancer (OvCA) present peritoneal disseminated disease at the time of diagnosis. During peritoneal metastasis, cancer cells detach from the primary tumor and disseminate through the intraperitoneal fluid. The peritoneal mesothelial cell (PMC) monolayer that lines the abdominal cavity is the first barrier encountered by OvCA cells. Subsequent progression of tumors through the peritoneum leads to the accumulation into the peritoneal stroma of a sizeable population of carcinoma-associated fibroblasts (CAFs), which is mainly originated from a mesothelial-to-mesenchymal transition (MMT) process. A common characteristic of OvCA patients is the intraperitoneal accumulation of ascitic fluid, which is composed of cytokines, chemokines, growth factors, miRNAs, and proteins contained in exosomes, as well as tumor and mesothelial suspended cells, among other components that vary in proportion between patients. Exosomes are small extracellular vesicles that have been shown to mediate peritoneal metastasis by educating a pre-metastatic niche, promoting the accumulation of CAFs via MMT, and inducing tumor growth and chemoresistance. This review summarizes and discusses the pivotal role of exosomes and MMT as mediators of OvCA peritoneal colonization and as emerging diagnostic and therapeutic targets. |
| doi_str_mv | 10.3390/ijms222111496 |
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During peritoneal metastasis, cancer cells detach from the primary tumor and disseminate through the intraperitoneal fluid. The peritoneal mesothelial cell (PMC) monolayer that lines the abdominal cavity is the first barrier encountered by OvCA cells. Subsequent progression of tumors through the peritoneum leads to the accumulation into the peritoneal stroma of a sizeable population of carcinoma-associated fibroblasts (CAFs), which is mainly originated from a mesothelial-to-mesenchymal transition (MMT) process. A common characteristic of OvCA patients is the intraperitoneal accumulation of ascitic fluid, which is composed of cytokines, chemokines, growth factors, miRNAs, and proteins contained in exosomes, as well as tumor and mesothelial suspended cells, among other components that vary in proportion between patients. Exosomes are small extracellular vesicles that have been shown to mediate peritoneal metastasis by educating a pre-metastatic niche, promoting the accumulation of CAFs via MMT, and inducing tumor growth and chemoresistance. This review summarizes and discusses the pivotal role of exosomes and MMT as mediators of OvCA peritoneal colonization and as emerging diagnostic and therapeutic targets.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms222111496</identifier><identifier>PMID: 34768926</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Abdomen ; Accumulation ; Ascites ; Ascitic fluid ; Ascitic Fluid - chemistry ; Ascitic Fluid - cytology ; Biosynthesis ; Carcinoma, Ovarian Epithelial - pathology ; Cell Line, Tumor ; Chemokines ; Chemoresistance ; Cytokines ; Cytokines - analysis ; Epithelial-Mesenchymal Transition - physiology ; Epithelium - pathology ; Exosomes ; Exosomes - metabolism ; Extracellular vesicles ; Female ; Fibroblasts ; Growth factors ; Humans ; Intercellular Signaling Peptides and Proteins - analysis ; Kinases ; Lipids ; Medical prognosis ; Mesenchyme ; Metastases ; Metastasis ; Mitochondrial DNA ; Ovarian cancer ; Ovarian Neoplasms - pathology ; Peritoneal Neoplasms - secondary ; Peritoneum ; Peritoneum - pathology ; Plasma ; Proteins ; Review ; Stroma ; Tumors</subject><ispartof>International journal of molecular sciences, 2021-10, Vol.22 (21), p.11496</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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During peritoneal metastasis, cancer cells detach from the primary tumor and disseminate through the intraperitoneal fluid. The peritoneal mesothelial cell (PMC) monolayer that lines the abdominal cavity is the first barrier encountered by OvCA cells. Subsequent progression of tumors through the peritoneum leads to the accumulation into the peritoneal stroma of a sizeable population of carcinoma-associated fibroblasts (CAFs), which is mainly originated from a mesothelial-to-mesenchymal transition (MMT) process. A common characteristic of OvCA patients is the intraperitoneal accumulation of ascitic fluid, which is composed of cytokines, chemokines, growth factors, miRNAs, and proteins contained in exosomes, as well as tumor and mesothelial suspended cells, among other components that vary in proportion between patients. Exosomes are small extracellular vesicles that have been shown to mediate peritoneal metastasis by educating a pre-metastatic niche, promoting the accumulation of CAFs via MMT, and inducing tumor growth and chemoresistance. 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During peritoneal metastasis, cancer cells detach from the primary tumor and disseminate through the intraperitoneal fluid. The peritoneal mesothelial cell (PMC) monolayer that lines the abdominal cavity is the first barrier encountered by OvCA cells. Subsequent progression of tumors through the peritoneum leads to the accumulation into the peritoneal stroma of a sizeable population of carcinoma-associated fibroblasts (CAFs), which is mainly originated from a mesothelial-to-mesenchymal transition (MMT) process. A common characteristic of OvCA patients is the intraperitoneal accumulation of ascitic fluid, which is composed of cytokines, chemokines, growth factors, miRNAs, and proteins contained in exosomes, as well as tumor and mesothelial suspended cells, among other components that vary in proportion between patients. 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| subjects | Abdomen Accumulation Ascites Ascitic fluid Ascitic Fluid - chemistry Ascitic Fluid - cytology Biosynthesis Carcinoma, Ovarian Epithelial - pathology Cell Line, Tumor Chemokines Chemoresistance Cytokines Cytokines - analysis Epithelial-Mesenchymal Transition - physiology Epithelium - pathology Exosomes Exosomes - metabolism Extracellular vesicles Female Fibroblasts Growth factors Humans Intercellular Signaling Peptides and Proteins - analysis Kinases Lipids Medical prognosis Mesenchyme Metastases Metastasis Mitochondrial DNA Ovarian cancer Ovarian Neoplasms - pathology Peritoneal Neoplasms - secondary Peritoneum Peritoneum - pathology Plasma Proteins Review Stroma Tumors |
| title | Mesothelial-to-Mesenchymal Transition and Exosomes in Peritoneal Metastasis of Ovarian Cancer |
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