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Tracking and Functional Characterization of Epithelial-Mesenchymal Transition and Mesenchymal Tumor Cells during Prostate Cancer Metastasis.

ABSTRACT: The epithelial-mesenchymal transition (EMT) has been postulated as a mechanism by which cancer cells acquire the invasive and stem-like traits necessary for distant metastasis. However, direct in vivo evidence for the role of EMT in the formation of cancer stem-like cells (CSC) and the metastatic cascade remains lacking. Here we report the first isolation and characterization of mesenchymal-like and EMT tumor cells, which harbor both epithelial and mesenchymal characteristics, in an autochthonous murine model of prostate cancer. By crossing the established Pb-Cre(+/-);Pten(L/L);Kras(G12D) (/+) prostate cancer model with a vimentin-GFP reporter strain, generating CPKV mice, we were able to isolate epithelial, EMT, and mesenchymal-like cancer cells based on expression of vimentin and EpCAM. CPKV mice (but not mice with Pten deletion alone) exhibited expansion of cells with EMT (EpCAM(+)/Vim-GFP(+)) and mesenchymal-like (EpCAM(-)/Vim-GFP(+)) characteristics at the primary tumor site and in circulation. These EMT and mesenchymal-like tumor cells displayed enhanced stemness and invasive character compared with epithelial tumor cells. Moreover, they displayed an enriched tumor-initiating capacity and could regenerate epithelial glandular structures in vivo, indicative of epithelia-mesenchyme plasticity. Interestingly, while mesenchymal-like tumor cells could persist in circulation and survive in the lung following intravenous injection, only epithelial and EMT tumor cells could form macrometastases. Our work extends the evidence that mesenchymal and epithelial states in cancer cells contribute differentially to their capacities for tumor initiation and metastatic seeding, respectively, and that EMT tumor cells exist with plasticity that can contribute to multiple stages of the metastatic cascade.

SUBMITTER: Ruscetti M

PROVIDER: S-EPMC4490048 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Tracking and Functional Characterization of Epithelial-Mesenchymal Transition and Mesenchymal Tumor Cells during Prostate Cancer Metastasis.

Ruscetti Marcus M Quach Bill B Dadashian Eman L EL Mulholland David J DJ Wu Hong H

Cancer research 20150506 13

The epithelial-mesenchymal transition (EMT) has been postulated as a mechanism by which cancer cells acquire the invasive and stem-like traits necessary for distant metastasis. However, direct in vivo evidence for the role of EMT in the formation of cancer stem-like cells (CSC) and the metastatic cascade remains lacking. Here we report the first isolation and characterization of mesenchymal-like and EMT tumor cells, which harbor both epithelial and mesenchymal characteristics, in an autochthonou ...[more]

PMID: 25948589

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Project description:Background and Objective Annexin A1 (annexin I, ANXA1), the first discovered member of the annexin superfamily, plays important roles in tumor development, invasion, metastasis, apoptosis and drug resistance based on tumor type-specific patterns of expression. The acquisition of the epithelial-mesenchymal transition (EMT) characteristics is an essential mechanism of metastasis because they increase the mobility and invasiveness of cancer cells. Cancer invasion and metastasis remain major health problems worldwide. Elucidating the role and mechanism of ANXA1 in the occurrence of EMT will help advance the development of novel therapeutic strategies. Hence, this review aims to attract everyone’s attention to the important role of ANXA1 in tumors and provide new ideas for clinical tumor treatment. Methods The PubMed database was mainly used to search for various English research papers and reviews related to the role of ANXA1 in tumors and EMT published from November 1994 to April 2022. The search terms used mainly include ANXA1, EMT, tumor, cancer, carcinoma, and mechanism. Key Content and Findings This article mainly provides a summary of the roles of ANXA1 and EMT in tumor metastasis as well as the various mechanisms via which ANXA1 facilitates the occurrence of EMT, thereby affecting tumor metastasis. In addition, the expression of ANXA1 in different metastatic tumor cell lines and its roles in tumorigenesis and development are also elaborated. This article has found many tumorous therapeutic targets related to ANXA1 and EMT, further confirming that ANXA1 has a huge potential for the diagnosis, treatment and prognosis of certain cancers. Conclusions Both the abnormal expression of ANXA1 and the occurrence of EMT are closely related to the invasion and metastasis of tumors, and more interestingly, ANXA1 can impact EMT directly or indirectly by mediating signaling pathways and adhesion among cells. We need more studies to elucidate the effects of ANXA1 on tumor invasion, migration and metastasis through EMT in vitro and in vivo clearly, and ultimately in patients to identify more therapeutic targets.

Dataset Information

Tracking and Functional Characterization of Epithelial-Mesenchymal Transition and Mesenchymal Tumor Cells during Prostate Cancer Metastasis.

Publications

Tracking and Functional Characterization of Epithelial-Mesenchymal Transition and Mesenchymal Tumor Cells during Prostate Cancer Metastasis.

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