Mesothelial-to-Mesenchymal Transition and Exosomes in Peritoneal Metastasis of Ovarian Cancer

Pascual-Antón, Lucía; Cardeñes, Beatriz; Cuesta, Ricardo Sáinz de la; González-Cortijo, Lucía; López–Cabrera, Manuel; Cabañas, Carlos; Sandoval, Pilar

doi:10.3390/ijms222111496

Cited by 48 publications

(30 citation statements)

References 151 publications

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“…In this regard, tumor-derived EVs facilitate the direct attachment of cancer cells to peritoneal mesothelial cells (PMCs) that line all peritoneal organs and structures, thus promoting the invasion of cancer cells through the mesothelial barrier. On the other hand, tumor-derived EVs induce the conversion of PMCs into cancer-associated fibroblasts (CAFs), which in turn, favor the survival, proliferation, and invasion of cancer cells, contributing to the metastatic process (reviewed in [ 12 , 13 , 14 , 15 ]). Importantly, tumor-derived EVs also mediate communication amongst cancer cells themselves, leading to the acquisition of a more aggressive and invasive phenotype, as well as conferring chemotherapy resistance [ 16 , 17 , 18 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…As stated above, tumor-derived EVs represent an important vehicle of communication amongst cancer cells in mediating the acquisition of a more invasive and/or chemoresistant phenotype, which is a hallmark of theses cancers with peritoneal dissemination [ 16 , 17 , 18 , 19 ]. On the other hand, the interactions (and uptake) of tumor-derived EVs with PMCs are also of crucial relevance in the process of peritoneal metastasis, as they facilitate the invasion of cancer cells through the mesothelial barrier and the conversion of PMCs into CAFs, which further fuels the metastatic process [ 12 , 13 , 14 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…Tumor-derived EVs are very abundant in the malignant ascites of CRC and OvC patients and have been shown to promote peritoneal metastasis through their specific interaction with—and uptake by—different immune and non-immune target cells in the peritoneal environment, in which they induce crucial phenotypic and functional changes involved in tumor progression and metastasis. In this regard, tumor-derived EVs cause immunosuppression and facilitate the direct attachment of cancer cells to peritoneal mesothelial cells (PMCs) that line all peritoneal structures, thus promoting the invasion of cancer cells through the mesothelium and the conversion of PMCs into cancer-associated fibroblasts (CAFs), which in turn, favor cancer-cell survival, proliferation, and invasion (reviewed in [ 12 , 13 , 14 , 15 ]). Importantly, tumor-derived EVs also mediate communication amongst cancer cells themselves.…”

Section: Introductionmentioning

confidence: 99%

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ALCAM/CD166 Is Involved in the Binding and Uptake of Cancer-Derived Extracellular Vesicles

Cardeñes

Clares

Bezos

et al. 2022

IJMS

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Colorectal cancer (CRC) and ovarian cancer (OvC) patients frequently develop peritoneal metastasis, a condition associated with a very poor prognosis. In these cancers, tumor-derived extracellular vesicles (EVs) cause immunosuppression, facilitate the direct attachment and invasion of cancer cells through the mesothelium, induce the conversion of peritoneal mesothelial cells (PMCs) into cancer-associated fibroblasts (CAFs) and transfer a more aggressive phenotype amongst cancer cells. Although the promoting role of EVs in CRC and OvC peritoneal metastasis is well established, the specific molecules that mediate the interactions between tumor-derived EVs and immune and non-immune target cells remain elusive. Here, we employed the SKOV-3 (ovarian adenocarcinoma) and Colo-320 (colorectal adenocarcinoma) human cell lines as model systems to study the interactions and uptake of EVs produced by ovarian carcinoma and colorectal carcinoma cells, respectively. We established that the adhesion molecule ALCAM/CD166 is involved in the interaction of cancer-derived EVs with recipient cancer cells (a process termed “EV binding” or “EV docking”) and in their subsequent uptake by these cells. The identification of ALCAM/CD166 as a molecule mediating the docking and uptake of CRC and OvC-derived EVs may be potentially exploited to block the peritoneal metastasis cascade promoted by EVs in CRC and OvC patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

ALCAM/CD166 Is Involved in the Binding and Uptake of Cancer-Derived Extracellular Vesicles

Cardeñes

Clares

Bezos

et al. 2022

IJMS

Self Cite

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“…MMT is the process by which mesothelial cells develop a more fibroblast-like phenotype and acquire the capacity to migrate and invade the submesothelial layer of the peritoneum. This process has been shown to be initiated by the presence of HGSOC and is a way for cancer cells to prepare the environment for easier adhesion and subsequent invasion ( 118 ). TGF-ß1 is considered the main factor secreted by HGSOC that initiates the induction of MMT ( 119 , 120 ).…”

Section: Microenvironment At Metastatic Nichesmentioning

confidence: 99%

The Transcoelomic Ecosystem and Epithelial Ovarian Cancer Dissemination

Ritch

Telleria

2022

Front. Endocrinol.

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Epithelial ovarian cancer (EOC) is considered the deadliest gynecological disease and is normally diagnosed at late stages, at which point metastasis has already occurred. Throughout disease progression, EOC will encounter various ecosystems and the communication between cancer cells and these microenvironments will promote the survival and dissemination of EOC. The primary tumor is thought to develop within the ovaries or the fallopian tubes, both of which provide a microenvironment with high risk of causing DNA damage and enhanced proliferation. EOC disseminates by direct extension from the primary tumors, as single cells or multicellular aggregates. Under the influence of cellular and non-cellular factors, EOC spheroids use the natural flow of peritoneal fluid to reach distant organs within the peritoneal cavity. These cells can then implant and seed distant organs or tissues, which develop rapidly into secondary tumor nodules. The peritoneal tissue and the omentum are two common sites of EOC metastasis, providing a microenvironment that supports EOC invasion and survival. Current treatment for EOC involves debulking surgery followed by platinum-taxane combination chemotherapy; however, most patients will relapse with a chemoresistant disease with tumors developed within the peritoneum. Therefore, understanding the role of the unique microenvironments that promote EOC transcoelomic dissemination is important in improving patient outcomes from this disease. In this review article, we address the process of ovarian cancer cellular fate at the site of its origin in the secretory cells of the fallopian tube or in the ovarian surface epithelial cells, their detachment process, how the cells survive in the peritoneal fluid avoiding cell death triggers, and how cancer- associated cells help them in the process. Finally, we report the mechanisms used by the ovarian cancer cells to adhere and migrate through the mesothelial monolayer lining the peritoneum. We also discuss the involvement of the transcoelomic ecosystem on the development of chemoresistance of EOC.

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“…PMCs can simultaneously express the epithelial marker cytokeratins and the mesothelial markers vimentin and desmin. They can also gradually transition to a mesenchymal phenotype and lose their epithelial phenotype when triggered by changes in the microenvironment, a phenomenon known as the mesothelial–mesenchymal transition (MMT) [ 5 , 6 ].…”

Section: Anatomical Physiological and Pathological Features Of Pmcsmentioning

confidence: 99%

Role of Peritoneal Mesothelial Cells in the Progression of Peritoneal Metastases

Guo

2022

Cancers

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Peritoneal metastatic cancer comprises a heterogeneous group of primary tumors that originate in the peritoneal cavity or metastasize into the peritoneal cavity from a different origin. Metastasis is a characteristic of end-stage disease, often indicative of a poor prognosis with limited treatment options. Peritoneal mesothelial cells (PMCs) are a thin layer of cells present on the surface of the peritoneum. They display differentiated characteristics in embryonic development and adults, representing the first cell layer encountering peritoneal tumors to affect their progression. PMCs have been traditionally considered a barrier to the intraperitoneal implantation and metastasis of tumors; however, recent studies indicate that PMCs can either inhibit or actively promote tumor progression through distinct mechanisms. This article presents a review of the role of PMCs in the progression of peritoneum implanted tumors, offering new ideas for therapeutic targets and related research.

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Mesothelial-to-Mesenchymal Transition and Exosomes in Peritoneal Metastasis of Ovarian Cancer

Cited by 48 publications

References 151 publications

ALCAM/CD166 Is Involved in the Binding and Uptake of Cancer-Derived Extracellular Vesicles

ALCAM/CD166 Is Involved in the Binding and Uptake of Cancer-Derived Extracellular Vesicles

The Transcoelomic Ecosystem and Epithelial Ovarian Cancer Dissemination

Role of Peritoneal Mesothelial Cells in the Progression of Peritoneal Metastases

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