scholarly journals Mesenchymal multipotent stromal cells and cancer safety: two sides of the same coin or a double-edged sword (review of foreign literature)

2021 ◽  
Vol 8 (1) ◽  
pp. 64-84
Author(s):  
D. A. Ivolgin ◽  
D. A. Kudlay
Keyword(s):  
Stromal Cells ◽  
Antitumor Agents ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapeutic Agents ◽  
Oncolytic Viruses ◽  
Antitumor Action ◽  
Malignant Neoplasms ◽  
Multipotent Stromal Cells ◽  
Mesenchymal Transition ◽  
Mesenchymal Multipotent Stromal Cells

Knowledge about the mechanisms of action of mesenchymal multipotent stromal cells (MSC) has undergone a significant evolution since their discovery. From the first attempts to use the remarkable properties of MSC in restoring the functions of organs and tissues, the most important question arose – how safe their use would be? One of the aspects of safety of the use of such biomaterial is tumorogenicity and oncogenicity. Numerous studies have shown that the mechanisms by which MSC realize their regenerative potential can, in principle, have a stimulating effect on tumor cells. This review presents specific mechanisms that have a potentially pro-tumor effect, which include the homing of MSC to the tumor site, support for replicative and proliferative signaling of both cancer cells and cancer stem cells, angiogenesis, and effects on the epithelial-mesenchymal transition. Along with pro-tumor mechanisms, the mechanisms of possible antitumor action are also described – direct suppression of tumor growth, loading and transportation of chemotherapeutic agents, oncolytic viruses, genetic modifications for targeting cancer, delivery of “suicide genes” to the tumor. Also, in conclusion, a small review of the current clinical trials of MSC as antitumor agents for malignant neoplasms of various localization (gastrointestinal tract, lungs, ovaries) is given. 

The Emerging Role of Metformin in the Prevention and Treatment of Colorectal Cancer: A Game Changer for Management of Colorectal Cancer

2021 ◽  
Vol 18 ◽  
Author(s):  
Moein Ala
Keyword(s):  
Colorectal Cancer ◽  
Intestinal Inflammation ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapeutic Agents ◽  
Advanced Adenoma ◽  
High Risk Population ◽  
Mesenchymal Transition ◽  
Cytotoxicity Activity ◽  
Increased Risk ◽  
Patients With Diabetes

: Metformin is an old, inexpensive and relatively safe anti-diabetic medication which can decrease the increased risk of several types of cancer in patients with diabetes. Recent meta-analyses revealed that metformin markedly decreased the incidence of colorectal adenoma, advanced adenoma and colorectal cancer (CRC) among patients with diabetes. Potential mechanisms by which metformin may decrease colorectal cancer risk include its effects on ameliorating intestinal inflammation and dysbiosis, suppressing major proliferative pathways, preventing DNA replication, accelerating tumor cells apoptosis, inhibiting intra-tumor angiogenesis and epithelial-mesenchymal transition (EMT), increasing tumor-infiltrating lymphocytes and CD68+ tumor-associated macrophages, and enhancing T cell cytotoxicity activity. It was uncovered that metformin can improve overall survival and CRC-specific survival among patients with diabetes and CRC. Interestingly, metformin decreased the incidence of colonic adenoma in patients with acromegaly and reduced the incidence of inflammatory bowel disease (IBD) among patients with diabetes, which can indirectly lower the risk of CRC. Results of phase II clinical trials revealed that metformin can enhance the anti-cancer effects of chemotherapeutic agents, such as 5-Fluorouracil (5-FU) and irinotecan on refractory CRC. Furthermore, metformin decreased the risk of new polyps and adenomas in patients without diabetes. Regarding the results of previous preclinical and clinical studies, it is rational to assess the effect of metformin in normoglycemic patients with CRC and expand its clinical application for treating CRC or preventing it in a high-risk population.

scholarly journals Exosomal miRNAs and lncRNAs: The Modulator Keys of Cancer-Associated Fibroblasts in the Genesis and Progression of Malignant Neoplasms

2021 ◽  
Vol 9 ◽  
Author(s):  
Julio César Villegas-Pineda ◽  
Mélida del Rosario Lizarazo-Taborda ◽  
Adrián Ramírez-de-Arellano ◽  
Ana Laura Pereira-Suárez
Keyword(s):  
Tumor Microenvironment ◽  
Epithelial Mesenchymal Transition ◽  
Future Perspective ◽  
Malignant Neoplasms ◽  
Cancer Associated Fibroblasts ◽  
Mesenchymal Transition ◽  
Relevant Evidence ◽  
State Of Research ◽  
Therapeutic Tools ◽  
Cellular Components

The tumor microenvironment is made up of a universe of molecular and cellular components that promote or inhibit the development of neoplasms. Among the molecular elements are cytokines, metalloproteinases, proteins, mitochondrial DNA, and nucleic acids, within which the ncRNAs: miRNAs and lncRNAs stand out due to their direct modulating effects on the genesis and progression of various cancers. Regarding cellular elements, the solid tumor microenvironment is made up of tumor cells, healthy adjacent epithelial cells, immune system cells, endothelial cells, and stromal cells, such as cancer-associated fibroblasts, which are capable of generating a modulating communication network with the other components of the tumor microenvironment through, among other mechanisms, the secretion of exosomal vesicles loaded with miRNAs and lncRNAs. These ncRNAs are key pieces in developing neoplasms since they have diverse effects on cancer cells and healthy cells, favoring or negatively regulating protumoral cellular events, such as migration, invasion, proliferation, metastasis, epithelial-mesenchymal transition, and resistance to treatment. Due to the growing number of relevant evidence in recent years, this work focused on reviewing, analyzing, highlighting, and showing the current state of research on exosomal ncRNAs derived from cancer-associated fibroblasts and their effects on different neoplasms. A future perspective on using these ncRNAs as real therapeutic tools in the treatment of cancer patients is also proposed.

scholarly journals Protein kinase C inhibitors override ZEB1-induced chemoresistance in HCC

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Rahul Sreekumar ◽  
Muhammad Emaduddin ◽  
Hajir Al-Saihati ◽  
Karwan Moutasim ◽  
James Chan ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Epithelial Mesenchymal Transition ◽  
Chemotherapeutic Agents ◽  
Tumour Cells ◽  
Mesenchymal Transition ◽  
Kinase C ◽  
Pkc Inhibitors ◽  
Hcc Cells

Abstract Epithelial–mesenchymal transition (EMT) is a process by which tumour cells lose epithelial characteristics, become mesenchymal and highly motile. EMT pathways also induce stem cell features and resistance to apoptosis. Identifying and targeting this pool of tumour cells is a major challenge. Protein kinase C (PKC) inhibition has been shown to eliminate breast cancer stem cells but has never been assessed in hepatocellular cancer (HCC). We investigated ZEB family of EMT inducer expression as a biomarker for metastatic HCC and evaluated the efficacy of PKC inhibitors for HCC treatment. We showed that ZEB1 positivity predicted patient survival in multiple cohorts and also validated as an independent biomarker of HCC metastasis. ZEB1-expressing HCC cell lines became resistant to conventional chemotherapeutic agents and were enriched in CD44high/CD24low cell population. ZEB1- or TGFβ-induced EMT increased PKCα abundance. Probing public databases ascertained a positive association of ZEB1 and PKCα expression in human HCC tumours. Inhibition of PKCα activity by small molecule inhibitors or by PKCA knockdown reduced viability of mesenchymal HCC cells in vitro and in vivo. Our results suggest that ZEB1 expression predicts survival and metastatic potential of HCC. Chemoresistant/mesenchymal HCC cells become addicted to PKC pathway and display sensitivity to PKC inhibitors such as UCN-01. Stratifying patients according to ZEB1 and combining UCN-01 with conventional chemotherapy may be an advantageous chemotherapeutic strategy.

scholarly journals Cripto-1 Promotes the Epithelial-Mesenchymal Transition in Esophageal Squamous Cell Carcinoma Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Chun Huang ◽  
Wangsheng Chen ◽  
Xiaowen Wang ◽  
Jinqiu Zhao ◽  
Qian Li ◽  
...  
Keyword(s):  
Esophageal Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Public Health Problem ◽  
Carcinoma Cells ◽  
Malignant Neoplasms ◽  
Major Public Health Problem ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
Tumorigenesis And Progression ◽  
Made In

Esophageal carcinoma is a major public health problem worldwide and one of the most aggressively malignant neoplasms. Although considerable diagnostic and therapeutic progress has been made in recent years, the prognosis of EC patients still remains dismal due to high rates of recurrence/metastasis and invasion. Previous studies have demonstrated that Epithelial mesenchymal transition (EMT) is proposed as a critical mechanism for the acquisition of malignant phenotypes by epithelial cells. Several lines of evidence have shown that Cripto-1 plays an important oncogenic role during tumorigenesis by promoting EMT. The aim of our study was to evaluate the significance of Cripto-1 which plays a role in EMT and its metastasis in esophageal carcinoma. Data of this study suggest that Cripto-1 overexpression is connected with the tumorigenesis and progression of esophageal carcinoma; shRNA might be feasible for the inhibition of the invasion and metastasis of esophageal carcinoma.

Differentiation of Mesenchymal Multipotent Stromal Cells of the Lungs in Pneumofibrosis

2013 ◽  
Vol 154 (4) ◽  
pp. 537-543 ◽  
Author(s):  
E. G. Skurikhin ◽  
E. S. Khmelevskaya ◽  
O. V. Pershina ◽  
N. N. Ermakova ◽  
V. A. Krupin ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Multipotent Stromal Cells ◽  
Mesenchymal Multipotent Stromal Cells

scholarly journals The Role of TWIST in Angiogenesis and Cell Migration in Giant Cell Tumor of Bone

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Shalini Singh ◽  
Isabella W. Y. Mak ◽  
Divya Handa ◽  
Michelle Ghert
Keyword(s):  
Cell Migration ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Stromal Cells ◽  
Epithelial Mesenchymal Transition ◽  
Cell Tumor ◽  
Stable Cell Line ◽  
Mesenchymal Transition

Giant cell tumor of bone (GCT) is a bone tumor consisting of numerous multinucleated osteoclastic giant cells involved in bone resorption and neoplastic osteoblast-like stromal cells responsible for tumor growth. The tumor occasionally metastasizes to the lung; however, factors leading to metastasis in this tumor are unknown. The TWIST-1 protein (also referred to as TWIST) has been suggested to be involved in epithelial-mesenchymal transition (EMT) and tumor progression in some cancers. In this study we investigated the functional role of TWIST in GCT cell angiogenesis and migration. Overexpression of TWIST in neoplastic GCT stromal cells significantly increased mRNA and protein expression of VEGF and VEGFR1 in vitro, whereas knockdown of TWIST resulted in decreased VEGF and VEGFR1 expression. A stable cell line with TWIST overexpression resulted in features of EMT including increased cell migration and downregulation of E-cadherin. The results of our study indicate that TWIST may play an important role in angiogenesis and cell migration in GCT.

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