scholarly journals Exosomes in Bone Sarcomas: Key Players in Metastasis

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 241 ◽  
Author(s):  
Mariona Chicón-Bosch ◽  
Oscar M. Tirado
Keyword(s):  
Tumour Progression ◽  
Survival Rates ◽  
Extracellular Vesicle ◽  
Poor Survival ◽  
Metastatic Phenotype ◽  
High Incidence ◽  
Key Players ◽  
Bone Sarcomas ◽  
Cellular Behaviour

Bone sarcomas are rare cancers which often present with metastatic disease and are still associated with poor survival rates. Studies in the last decade have identified that exosomes, a type of extracellular vesicle released by cells, play an important role in tumour progression and dissemination. Through the transfer of their cargo (RNAs, proteins, and lipids) across cells, they are involved in cellular cross-talk and can induce changes in cellular behaviour. Exosomes have been shown to be important in metastasis organotropism, induction of angiogenesis and vascular permeability, the education of cells towards a pro-metastatic phenotype or the interaction between stromal and tumour cells. Due to the importance exosomes have in disease progression and the high incidence of metastasis in bone sarcomas, recent studies have evaluated the implications of these extracellular vesicles in bone sarcomas. In this review, we discuss the studies that evaluate the role of exosomes in osteosarcoma, Ewing sarcoma, and preliminary data on chondrosarcoma.

scholarly journals Notch-Jagged signalling can give rise to clusters of cells exhibiting a hybrid epithelial/mesenchymal phenotype

2016 ◽  
Vol 13 (118) ◽  
pp. 20151106 ◽  
Author(s):  
Marcelo Boareto ◽  
Mohit Kumar Jolly ◽  
Aaron Goldman ◽  
Mika Pietilä ◽  
Sendurai A. Mani ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Tumour Progression ◽  
Cell Communication ◽  
Notch Signalling ◽  
Circulating Tumour Cells ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition ◽  
Mesenchymal To Epithelial Transition ◽  
Key Players

Metastasis can involve repeated cycles of epithelial-to-mesenchymal transition (EMT) and its reverse mesenchymal-to-epithelial transition. Cells can also undergo partial transitions to attain a hybrid epithelial/mesenchymal (E/M) phenotype that allows the migration of adhering cells to form a cluster of circulating tumour cells. These clusters can be apoptosis-resistant and possess an increased metastatic propensity as compared to the cells that undergo a complete EMT (mesenchymal cells). Hence, identifying the key players that can regulate the formation and maintenance of such clusters may inform anti-metastasis strategies. Here, we devise a mechanism-based theoretical model that links cell–cell communication via Notch-Delta-Jagged signalling with the regulation of EMT. We demonstrate that while both Notch-Delta and Notch-Jagged signalling can induce EMT in a population of cells, only Jagged-dominated Notch signalling, but not Delta-dominated signalling, can lead to the formation of clusters containing hybrid E/M cells. Our results offer possible mechanistic insights into the role of Jagged in tumour progression, and offer a framework to investigate the effects of other microenvironmental signals during metastasis.

scholarly journals Oncogenic role of SFRP2 in p53-mutant osteosarcoma development via autocrine and paracrine mechanism

2018 ◽  
Vol 115 (47) ◽  
pp. E11128-E11137 ◽  
Author(s):  
Huensuk Kim ◽  
Seungyeul Yoo ◽  
Ruoji Zhou ◽  
An Xu ◽  
Jeffrey M. Bernitz ◽  
...  
Keyword(s):  
Survival Rates ◽  
P53 Mutation ◽  
Poor Survival ◽  
Independent Manner ◽  
Li Fraumeni Syndrome ◽  
Primary Bone Tumor ◽  
Tumorigenic Potential ◽  
Normal Osteoblast ◽  
Induced Pluripotent

Osteosarcoma (OS), the most common primary bone tumor, is highly metastatic with high chemotherapeutic resistance and poor survival rates. Using induced pluripotent stem cells (iPSCs) generated from Li–Fraumeni syndrome (LFS) patients, we investigate an oncogenic role of secreted frizzled-related protein 2 (SFRP2) in p53 mutation-associated OS development. Interestingly, we find that high SFRP2 expression in OS patient samples correlates with poor survival. Systems-level analyses identified that expression of SFRP2 increases during LFS OS development and can induce angiogenesis. Ectopic SFRP2 overexpression in normal osteoblast precursors is sufficient to suppress normal osteoblast differentiation and to promote OS phenotypes through induction of oncogenic molecules such as FOXM1 and CYR61 in a β-catenin–independent manner. Conversely, inhibition of SFRP2, FOXM1, or CYR61 represses the tumorigenic potential. In summary, these findings demonstrate the oncogenic role of SFRP2 in the development of p53 mutation-associated OS and that inhibition of SFRP2 is a potential therapeutic strategy.

scholarly journals Therapeutically Significant MicroRNAs in Primary and Metastatic Brain Malignancies

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2534 ◽  
Author(s):  
Akilandeswari A. Balachandran ◽  
Leon M. Larcher ◽  
Suxiang Chen ◽  
Rakesh N. Veedu
Keyword(s):  
Brain Tumors ◽  
High Mortality ◽  
Survival Rates ◽  
Primary Brain Tumor ◽  
Metastatic Brain Tumors ◽  
Poor Survival ◽  
Aggressive Form ◽  
Targeted Treatments ◽  
The Given

Brain cancer is one among the rare cancers with high mortality rate that affects both children and adults. The most aggressive form of primary brain tumor is glioblastoma. Secondary brain tumors most commonly metastasize from primary cancers of lung, breast, or melanoma. The five-year survival of primary and secondary brain tumors is 34% and 2.4%, respectively. Owing to poor prognosis, tumor heterogeneity, increased tumor relapse, and resistance to therapies, brain cancers have high mortality and poor survival rates compared to other cancers. Early diagnosis, effective targeted treatments, and improved prognosis have the potential to increase the survival rate of patients with primary and secondary brain malignancies. MicroRNAs (miRNAs) are short noncoding RNAs of approximately 18–22 nucleotides that play a significant role in the regulation of multiple genes. With growing interest in the development of miRNA-based therapeutics, it is crucial to understand the differential role of these miRNAs in the given cancer scenario. This review focuses on the differential expression of ten miRNAs (miR-145, miR-31, miR-451, miR-19a, miR-143, miR-125b, miR-328, miR-210, miR-146a, and miR-126) in glioblastoma and brain metastasis. These miRNAs are highly dysregulated in both primary and metastatic brain tumors, which necessitates a better understanding of their role in these cancers. In the context of the tumor microenvironment and the expression of different genes, these miRNAs possess both oncogenic and/or tumor-suppressive roles within the same cancer.

scholarly journals Roles of Non-Coding RNAs on Anaplastic Thyroid Carcinomas

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3159
Author(s):  
Plabon Kumar Das ◽  
Saharia Yeasmin Asha ◽  
Ichiro Abe ◽  
Farhadul Islam ◽  
Alfred K. Lam
Keyword(s):  
Gene Expression ◽  
Tumour Progression ◽  
Regulation Of Gene Expression ◽  
Survival Rates ◽  
Human Leukocyte ◽  
Anaplastic Thyroid Cancer ◽  
Therapeutic Interventions ◽  
Poor Survival ◽  
Human Carcinomas ◽  
Non Coding Rnas

Anaplastic thyroid cancer (ATC) remains as one of the most aggressive human carcinomas with poor survival rates in patients with the cancer despite therapeutic interventions. Novel targeted and personalized therapies could solve the puzzle of poor survival rates of patients with ATC. In this review, we discuss the role of non-coding RNAs in the regulation of gene expression in ATC as well as how the changes in their expression could potentially reshape the characteristics of ATCs. A broad range of miRNA, such as miR-205, miR-19a, miR-17-3p and miR-17-5p, miR-618, miR-20a, miR-155, etc., have abnormal expressions in ATC tissues and cells when compared to those of non-neoplastic thyroid tissues and cells. Moreover, lncRNAs, such as H19, Human leukocyte antigen (HLA) complex P5 (HCP5), Urothelial carcinoma-associated 1 (UCA1), Nuclear paraspeckle assembly transcript 1 (NEAT1), etc., participate in transcription and post-transcriptional regulation of gene expression in ATC cells. Dysregulations of these non-coding RNAs were associated with development and progression of ATC by modulating the functions of oncogenes during tumour progression. Thus, restoration of the abnormal expression of these miRNAs and lncRNAs may serve as promising ways to treat the patients with ATC. In addition, siRNA mediated inhibition of several oncogenes may act as a potential option against ATC. Thus, non-coding RNAs can be useful as prognostic biomarkers and potential therapeutic targets for the better management of patients with ATC.

scholarly journals USP1 Promotes GC Metastasis via Stabilizing ID2

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Nuoya Li ◽  
Lei Wu ◽  
Xingye Zuo ◽  
Huilong Luo ◽  
Yanling Sheng ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Survival Rates ◽  
Underlying Mechanism ◽  
Poor Survival ◽  
Cellular Analysis ◽  
Potential Biomarker ◽  
Therapy Target

Gastric cancer (GC) is one of the most common malignant tumors all over the world. And recurrence and metastasis are still the main causes of low survival rate for advanced GC. USP1 has been shown overexpressed in multiple cancers, which indicate its important biomarker in tumorigenesis and development. Our study is aimed at defining the exact role of USP1 on GC metastasis and the underlying mechanism. USP1 was firstly found overexpressed in GC tissues and relatively high-expression levels conferred poor survival rates. Then, real-time cellular analysis (RTCA) showed that USP1 knockdown inhibited GC metastasis both in vitro and in vivo. Mechanically, we demonstrated that USP1 promoted GC metastasis via upregulating ID2 expression and further confirmed that USP1 stabilized ID2 expression through deubiquitinating ID2 in GC. In conclusion, our study showed that USP1 promoted GC metastasis via stabilizing ID2 expression, which provides a potential biomarker and therapy target for GC.

scholarly journals Oncogenic role of sFRP2 in P53-mutant osteosarcoma development via autocrine and paracrine mechanism

2018 ◽  
Author(s):  
Huen Suk Kim ◽  
Seungyeul Yoo ◽  
Jeffrey M. Bernitz ◽  
Ye Yuan ◽  
Andreia M. Gomes ◽  
...  
Keyword(s):  
Survival Rates ◽  
P53 Mutation ◽  
Poor Survival ◽  
Independent Manner ◽  
Li Fraumeni Syndrome ◽  
Primary Bone Tumor ◽  
Tumorigenic Potential ◽  
Normal Osteoblast ◽  
Induced Pluripotent

AbstractOsteosarcoma (OS), the most common primary bone tumor, is highly metastatic with high chemotherapeutic resistance and poor survival rates. Using induced pluripotent stem cells (iPSCs) generated from Li-Fraumeni syndrome (LFS) patients, we investigated an oncogenic role of secreted frizzled-related protein 2 (sFRP2) in P53 mutation-associated OS development. Interestingly, we found that high sFRP2 expression in OS patient samples correlates with poor survival. Systems-level analyses identified that expression of sFRP2 increases during LFS OS development and can induce angiogenesis. Ectopic sFRP2 overexpression in normal osteoblast precursors is sufficient to suppress normal osteoblast differentiation and to promote OS phenotypes through induction of oncogenic molecules such as FOXM1 and CYR61 in a β-catenin independent manner. Conversely, inhibition of sFRP2, FOXM1 or CYR61 represses the tumorigenic potential. In summary, these findings demonstrate the oncogenic role of sFRP2 in P53 mutation-associated OS development and that inhibition of sFRP2 is a potential therapeutic strategy.

scholarly journals Circulating MicroRNAs as Novel Potential Diagnostic Biomarkers for Osteosarcoma: A Systematic Review

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1432
Author(s):  
Thaís Borges Gally ◽  
Milena Magalhães Aleluia ◽  
Grasiely Faccin Borges ◽  
Carla Martins Kaneto
Keyword(s):  
Systematic Review ◽  
Survival Rates ◽  
Diagnostic Methods ◽  
Circulating Mirnas ◽  
Circulating Micrornas ◽  
Non Invasive ◽  
High Incidence ◽  
Novel Biomarkers ◽  
Number Of Publications

Osteosarcoma (OS) is a fast-progressing bone tumor with high incidence in children and adolescents. The main diagnostic methods for OS are imaging exams and biopsies. In spite of the several resources available for detecting the disease, establishing an early diagnosis is still difficult, resulting in worse prognosis and lower survival rates for patients with OS. The identification of novel biomarkers would be helpful, and recently, circulating microRNAs (miRNAs) have been pointed to as possible non-invasive biomarkers. In order to assess the effectiveness of miRNA research, we performed a systematic review to assess the potential role of circulating miRNAs as biomarkers for OS diagnosis. We performed a search in various databases—PubMed, LILACS (Literatura Latino-americana e do Caribe em Ciências da Saúde), VHL (Virtual Health Library), Elsevier, Web of Science, Gale Academic One File—using the terms: “Circulating microRNAs” OR “plasma microRNAs” OR “serum microRNAs” OR “blood microRNAs” OR “cell-free microRNAs” OR “exosome microRNAs” OR “extracellular vesicles microRNAs” OR “liquid biopsy” AND “osteosarcoma” AND “diagnostic”. We found 35 eligible studies that were independently identified and had had their quality assessed according to Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines. Despite the useful number of publications on this subject and the fact that several microRNAs showed excellent diagnostic performance for OS, the lack of consistency in results suggests that additional prospective studies are needed to confirm the role of circulating miRNAs as non-invasive biomarkers in OS.

scholarly journals Inflammation and Epithelial-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma: Fighting Against Multiple Opponents

2017 ◽  
Vol 10 ◽  
pp. 117906441770928 ◽  
Author(s):  
Farid G Khalafalla ◽  
Mohammad W Khan
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Survival Rates ◽  
Ductal Adenocarcinoma ◽  
Poor Survival ◽  
Inflammatory Signaling ◽  
Mesenchymal Transition ◽  
Enhanced Resistance ◽  
Resistance To Chemotherapy

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and one of the most lethal human cancers. Inflammation is a critical component in PDAC initiation and progression. Inflammation also contributes to the aggressiveness of PDAC indirectly via induction of epithelial-mesenchymal transition (EMT), altogether leading to enhanced resistance to chemotherapy and poor survival rates. This review gives an overview of the key pro-inflammatory signaling pathways involved in PDAC pathogenesis and discusses the role of inflammation in induction of EMT and development of chemoresistance in patients with PDAC.

Acid ceramidase, a double-edged sword in cancer aggression: A minireview

2020 ◽  
Vol 20 ◽  
Author(s):  
Helen Shiphrah Vethakanraj ◽  
Niveditha Chandrasekaran ◽  
Ashok Kumar Sekar
Keyword(s):  
Cell Fate ◽  
Cancer Progression ◽  
Potential Role ◽  
Tumour Progression ◽  
Acid Ceramidase ◽  
The Core ◽  
The Past ◽  
Sphingosine 1 Phosphate ◽  
Key Enzyme

: Acid ceramidase (AC), the key enzyme of the ceramide metabolic pathway hydrolyzes pro-apoptotic ceramide to sphingosine, which by the action of sphingosine-1-kinase is metabolized to mitogenic sphingosine-1-phosphate. The intracellular level of AC determines ceramide/sphingosine-1-phosphate rheostat which in turn decides the cell fate. The upregulated AC expression during cancerous condition acts as a “double-edged sword” by converting pro-apoptotic ceramide to anti-apoptotic sphingosine-1-phosphate, wherein on one end, the level of ceramide is decreased and on the other end, the level of sphingosine-1-phosphate is increased, thus altogether aggravating the cancer progression. In addition, cancer cells with upregulated AC expression exhibited increased cell proliferation, metastasis, chemoresistance, radioresistance and numerous strategies were developed in the past to effectively target the enzyme. Gene silencing and pharmacological inhibition of AC sensitized the resistant cells to chemo/radiotherapy thereby promoting cell death. The core objective of this review is to explore AC mediated tumour progression and the potential role of AC inhibitors in various cancer cell lines/models.

Role of MicroRNAs in Colon Cancer Progression and Metastasis

2020 ◽  
Vol 20 ◽  
Author(s):  
Shruthi Sanjitha Sampath ◽  
Sivaramakrishnan Venkatabalsubramanian ◽  
Satish Ramalingam
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Target Genes ◽  
Tumour Progression ◽  
Intestinal Barrier ◽  
Colon Cancer Progression ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Novel Therapeutic Strategies

: MicroRNAs regulate gene expression at the posttranscriptional level by binding to the mRNA of their target genes. The dysfunction of miRNAs is strongly associated with the inflammation of the colon. Besides, some microRNAs are shown to suppress tumours while others promote tumour progression and metastasis. Inflammatory bowel diseases include Crohn’s disease and Ulcerative colitis which increase the risk factor for inflammation-associated colon cancer. MicroRNAs are shown to be involved in gastrointestinal pathologies, by targeting the transcripts encoding proteins of the intestinal barrier and their regulators that are associated with inflammation and colon cancer. Detection of these microRNAs in the blood, serum, tissues, faecal matter, etc will enable us to use these microRNAs as biomarkers for early detection of the associated malignancies and design novel therapeutic strategies to overcome the same. Information on MicroRNAs can be applied for the development of targeted therapies against inflammation-mediated colon cancer.

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