scholarly journals Probing single-cell metabolism reveals prognostic value of highly metabolically active circulating stromal cells in prostate cancer

2020 ◽  
Vol 6 (40) ◽  
pp. eaaz3849
Author(s):  
Francesca Rivello ◽  
Kinga Matuła ◽  
Aigars Piruska ◽  
Minke Smits ◽  
Niven Mehra ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Single Cell ◽  
Cancer Patients ◽  
Stromal Cells ◽  
Metastatic Prostate Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Therapy Response ◽  
Sequencing Analysis ◽  
Label Free ◽  
Mesenchymal Transition

Despite their important role in metastatic disease, no general method to detect circulating stromal cells (CStCs) exists. Here, we present the Metabolic Assay-Chip (MA-Chip) as a label-free, droplet-based microfluidic approach allowing single-cell extracellular pH measurement for the detection and isolation of highly metabolically active cells (hm-cells) from the tumor microenvironment. Single-cell mRNA-sequencing analysis of the hm-cells from metastatic prostate cancer patients revealed that approximately 10% were canonical EpCAM+ hm-CTCs, 3% were EpCAM− hm-CTCs with up-regulation of prostate-related genes, and 87% were hm-CStCs with profiles characteristic for cancer-associated fibroblasts, mesenchymal stem cells, and endothelial cells. Kaplan-Meier analysis shows that metastatic prostate cancer patients with more than five hm-cells have a significantly poorer survival probability than those with zero to five hm-cells. Thus, prevalence of hm-cells is a prognosticator of poor outcome in prostate cancer, and a potentially predictive and therapy response biomarker for agents cotargeting stromal components and preventing epithelial-to-mesenchymal transition.

scholarly journals Role of MicroRNAs in Treatment Response in Prostate Cancer

2018 ◽  
Vol 18 (10) ◽  
pp. 929-944 ◽  
Author(s):  
Anshuli Razdan ◽  
Paul de Souza ◽  
Tara Laurine Roberts
Keyword(s):  
Prostate Cancer ◽  
Disease Progression ◽  
Treatment Response ◽  
Cancer Patients ◽  
Epithelial To Mesenchymal Transition ◽  
Therapy Response ◽  
Predictive Biomarkers ◽  
Mortality And Morbidity ◽  
Mesenchymal Transition ◽  
Cell Growth And Proliferation

Prostate cancer (PCa) is the most common non-skin cancer in men worldwide, resulting in significant mortality and morbidity. Depending on the grade and stage of the cancer, patients may be given radiation therapy, hormonal therapy, or chemotherapy. However, more than half of these patients develop resistance to treatment, leading to disease progression and metastases, often with lethal consequences. MicroRNAs (miRNAs) are short, non-coding RNAs, which regulate numerous physiological as well as pathological processes, including cancer. miRNAs mediate their regulatory effect predominately by binding to the 3′-untranslated region (UTR) of their target mRNAs. In this review, we will describe the mechanisms by which miRNAs mediate resistance to radiation and drug therapy (i.e. hormone therapy and chemotherapy) in PCa, including control of apoptosis, cell growth and proliferation, autophagy, epithelial-to-mesenchymal transition (EMT), invasion and metastasis, and cancer stem cells (CSCs). Furthermore, we will discuss the utility of circulating miRNAs isolated from different body fluids of prostate cancer patients as non-invasive biomarkers of cancer detection, disease progression, and therapy response. Finally, we will shortlist the candidate miRNAs, which may have a role in drug and radioresistance, that could potentially be used as predictive biomarkers of treatment response.

scholarly journals Glycidamide Promotes the Growth and Migratory Ability of Prostate Cancer Cells by Changing the Protein Expression of Cell Cycle Regulators and Epithelial-to-Mesenchymal Transition (EMT)-Associated Proteins with Prognostic Relevance

2019 ◽  
Vol 20 (9) ◽  
pp. 2199
Author(s):  
Titus Ime Ekanem ◽  
Chi-Chen Huang ◽  
Ming-Heng Wu ◽  
Ding-Yen Lin ◽  
Wen-Fu T. Lai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Protein Expression ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Epithelial To Mesenchymal Transition ◽  
Gene Signature ◽  
Prostate Cancer Cells ◽  
Mesenchymal Transition ◽  
Prognostic Relevance

Acrylamide (AA) and glycidamide (GA) can be produced in carbohydrate-rich food when heated at a high temperature, which can induce a malignant transformation. It has been demonstrated that GA is more mutagenic than AA. It has been shown that the proliferation rate of some cancer cells are increased by treatment with GA; however, the exact genes that are induced by GA in most cancer cells are not clear. In the present study, we demonstrated that GA promotes the growth of prostate cancer cells through induced protein expression of the cell cycle regulator. In addition, we also found that GA promoted the migratory ability of prostate cancer cells through induced epithelial-to-mesenchymal transition (EMT)-associated protein expression. In order to understand the potential prognostic relevance of GA-mediated regulators of the cell cycle and EMT, we present a three-gene signature to evaluate the prognosis of prostate cancer patients. Further investigations suggested that the three-gene signature (CDK4, TWIST1 and SNAI2) predicted the chances of survival better than any of the three genes alone for the first time. In conclusion, we suggested that the three-gene signature model can act as marker of GA exposure. Hence, this multi-gene panel may serve as a promising outcome predictor and potential therapeutic target in prostate cancer patients.

scholarly journals Organoid and Primary Epithelial Cultures of Human Prostate Show the Key Role of the Epithelial-to-Mesenchymal Transition in Generation of Tissue-Specific Stromal Cells

2021 ◽  
Author(s):  
V. M. Ryabov ◽  
A. O. Georgieva ◽  
M. A. Voskresensky ◽  
B. K. Komyakov ◽  
O. V. Rogoza ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Stromal Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Cells ◽  
Spontaneous Transformation ◽  
Homogeneous Population ◽  
Tissue Specific ◽  
Mesenchymal Transition ◽  
Organoid Cultures

Abstract The prostate gland (PG) is a small organ in the male reproductive system that is currently the focus of biomedical research due to its leading position in morbidity and mortality from the tissue-specific prostate cancer (PC). The PG epithelium, which undergoes a cancerous transformation, is formed and functions under the control of androgens. At the beginning of the disease, epithelial cells produce an androgen receptor (AR) and are sensitive to androgen-deprivation therapy. However, such therapy inevitably leads to the transition of the disease to the castration-resistant prostate cancer (CRPC), which manifests itself in metastasis and rapid mortality. In CRPC, the cells of the prostate epithelium change their phenotype, that may be associated with AR mutation and loss the sensitivity to specific therapy. The mechanism of PG phenotypic transformation may be hidden in the interaction and formation of the stromal and epithelial cells, which are evident during the establishment of the primary cultures. The aim of this study was to investigate the generation of human PG stromal cells in primary stromal and organoid cultures. We found that, in contrast to the rapid appearance and formation of a homogeneous population of mesenchymal cells in primary stromal cultures of most tissues, human PG cell cultures are formed initially from epithelial cells. They appear in the second week of cultivation and produce cytokeratins (CKs). A homogeneous population of mesenchymal cells producing vimentin is formed only at the end of the fourth week of cultivation. It is accompanied by the disappearance of epithelial cells. At the same time, some epithelial cells simultaneously produce CKs and vimentin. In PG organoid cultures, there is often a concomitant growth of epithelial, but not mesenchymal, cells on culture plastic. During the cultivation of epithelial cells arising from the organoid cultures, they, like the cells of the primary epithelium, exhibit the ability to spontaneous transformation into mesenchymal cells and simultaneously produce CKs and vimentin. Our data suggest that in primary and organoid PG cultures, stromal cells can be formed from epithelium due to the epithelial-to-mesenchymal transition (EMT). The tendency of PG epithelium toward spontaneous EMT may contribute to the mechanism of high sensitivity of prostate tissue to malignant transformation and metastasis. Understanding this mechanism may contribute to the development of effective antitumor therapy of prostate cancer.

scholarly journals CdGAP promotes prostate cancer metastasis by regulating epithelial-to-mesenchymal transition, cell cycle progression, and apoptosis

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Chahat Mehra ◽  
Ji-Hyun Chung ◽  
Yi He ◽  
Mónica Lara-Márquez ◽  
Marie-Anne Goyette ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cancer Patients ◽  
Cell Cycle Progression ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Migration And Invasion ◽  
Cycle Progression ◽  
Mesenchymal Transition ◽  
Potential Biomarker

AbstractHigh mortality of prostate cancer patients is primarily due to metastasis. Understanding the mechanisms controlling metastatic processes remains essential to develop novel therapies designed to prevent the progression from localized disease to metastasis. CdGAP plays important roles in the control of cell adhesion, migration, and proliferation, which are central to cancer progression. Here we show that elevated CdGAP expression is associated with early biochemical recurrence and bone metastasis in prostate cancer patients. Knockdown of CdGAP in metastatic castration-resistant prostate cancer (CRPC) PC-3 and 22Rv1 cells reduces cell motility, invasion, and proliferation while inducing apoptosis in CdGAP-depleted PC-3 cells. Conversely, overexpression of CdGAP in DU-145, 22Rv1, and LNCaP cells increases cell migration and invasion. Using global gene expression approaches, we found that CdGAP regulates the expression of genes involved in epithelial-to-mesenchymal transition, apoptosis and cell cycle progression. Subcutaneous injection of CdGAP-depleted PC-3 cells into mice shows a delayed tumor initiation and attenuated tumor growth. Orthotopic injection of CdGAP-depleted PC-3 cells reduces distant metastasic burden. Collectively, these findings support a pro-oncogenic role of CdGAP in prostate tumorigenesis and unveil CdGAP as a potential biomarker and target for prostate cancer treatments.

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