scholarly journals Interplay between Inflammation and Stemness in Cancer Cells: The Role of Toll-Like Receptor Signaling

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Da-Wei Yeh ◽  
Li-Rung Huang ◽  
Ya-Wen Chen ◽  
Chi-Ying F. Huang ◽  
Tsung-Hsien Chuang
Keyword(s):  
Cancer Treatment ◽  
Cancer Cells ◽  
Feedback Loop ◽  
Cancer Metastasis ◽  
Inflammatory Responses ◽  
Treatment Resistance ◽  
Small Population ◽  
Tlr Signaling ◽  
Intrinsic Factors

Cancer stem cells (CSCs) are a small population of cancer cells that exhibit stemness. These cells contribute to cancer metastasis, treatment resistance, and relapse following therapy; therefore, they may cause malignancy and reduce the success of cancer treatment. Nuclear factor kappa B- (NF-κB-) mediated inflammatory responses increase stemness in cancer cells, and CSCs constitutively exhibit higher NF-κB activation, which in turn increases their stemness. These opposite effects form a positive feedback loop that further amplifies inflammation and stemness in cancer cells, thereby expanding CSC populations in the tumor. Toll-like receptors (TLRs) activate NF-κB-mediated inflammatory responses when stimulated by carcinogenic microbes and endogenous molecules released from cells killed during cancer treatment. NF-κB activation by extrinsic TLR ligands increases stemness in cancer cells. Moreover, it was recently shown that increased NF-κB activity and inflammatory responses in CSCs may be caused by altered TLR signaling during the enrichment of stemness in cancer cells. Thus, the activation of TLR signaling by extrinsic and intrinsic factors drives a positive interplay between inflammation and stemness in cancer cells.

scholarly journals The Role of Platelets in the Tumor-Microenvironment and the Drug Resistance of Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 240 ◽  
Author(s):  
Phung Huong ◽  
Lap Nguyen ◽  
Xuan-Bac Nguyen ◽  
Sang Lee ◽  
Duc-Hiep Bach
Keyword(s):  
Drug Resistance ◽  
Growth Factors ◽  
Tumor Microenvironment ◽  
Treatment Failure ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Chemotherapeutic Drugs ◽  
Activated Platelets

Besides the critical functions in hemostasis, thrombosis and the wounding process, platelets have been increasingly identified as active players in various processes in tumorigenesis, including angiogenesis and metastasis. Once activated, platelets can release bioactive contents such as lipids, microRNAs, and growth factors into the bloodstream, subsequently enhancing the platelet–cancer interaction and stimulating cancer metastasis and angiogenesis. The mechanisms of treatment failure of chemotherapeutic drugs have been investigated to be associated with platelets. Therefore, understanding how platelets contribute to the tumor microenvironment may potentially identify strategies to suppress cancer angiogenesis, metastasis, and drug resistance. Herein, we present a review of recent investigations on the role of platelets in the tumor-microenvironment including angiogenesis, and metastasis, as well as targeting platelets for cancer treatment, especially in drug resistance.

Potential of Mesenchymal Stem Cells in Anti-Cancer Therapies

2020 ◽  
Vol 15 (6) ◽  
pp. 482-491 ◽  
Author(s):  
Milena Kostadinova ◽  
Milena Mourdjeva
Keyword(s):  
Cancer Cells ◽  
Small Population ◽  
Tumor Formation ◽  
Bioactive Molecules ◽  
Cancer Therapies ◽  
New Methods ◽  
Cycle Arrest ◽  
Anti Cancer ◽  
Blocking Mechanisms

Mesenchymal stem/stromal cells (MSCs) are localized throughout the adult body as a small population in the stroma of the tissue concerned. In injury, tissue damage, or tumor formation, they are activated and leave their niche to migrate to the site of injury, where they release a plethora of growth factors, cytokines, and other bioactive molecules. With the accumulation of data about the interaction between MSCs and tumor cells, the dualistic role of MSCs remains unclear. However, a large number of studies have demonstrated the natural anti-tumor properties inherent in MSCs, so this is the basis for intensive research for new methods using MSCs as a tool to suppress cancer cell development. This review focuses specifically on advanced approaches in modifying MSCs to become a powerful, precision- targeted tool for killing cancer cells, but not normal healthy cells. Suppression of tumor growth by MSCs can be accomplished by inducing apoptosis or cell cycle arrest, suppressing tumor angiogenesis, or blocking mechanisms mediating metastasis. In addition, the chemosensitivity of cancer cells may be increased so that the dose of the chemotherapeutic agent used could be significantly reduced.

scholarly journals Therapeutic Targeting of Epithelial Plasticity Programs: Focus on the Epithelial-Mesenchymal Transition

2017 ◽  
Vol 203 (2) ◽  
pp. 114-127 ◽  
Author(s):  
Reem Malek ◽  
Hailun Wang ◽  
Kekoa Taparra ◽  
Phuoc T. Tran
Keyword(s):  
Cancer Cells ◽  
Regulatory Networks ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
Therapeutic Targets ◽  
Treatment Resistance ◽  
Mesenchymal Transition ◽  
Epithelial Plasticity ◽  
Canonical Pathways

Mounting data points to epithelial plasticity programs such as the epithelial-mesenchymal transition (EMT) as clinically relevant therapeutic targets for the treatment of malignant tumors. In addition to the widely realized role of EMT in increasing cancer cell invasiveness during cancer metastasis, the EMT has also been implicated in allowing cancer cells to avoid tumor suppressor pathways during early tumorigenesis. In addition, data linking EMT to innate and acquired treatment resistance further points towards the desire to develop pharmacological therapies to target epithelial plasticity in cancer. In this review we organized our discussion on pathways and agents that can be used to target the EMT in cancer into 3 groups: (1) extracellular inducers of EMT, (2) the transcription factors that orchestrate the EMT transcriptome, and (3) the downstream effectors of EMT. We highlight only briefly specific canonical pathways known to be involved in EMT, such as the signal transduction pathways TGFβ, EFGR, and Axl-Gas6. We emphasize in more detail pathways that we believe are emerging novel pathways and therapeutic targets such as epigenetic therapies, glycosylation pathways, and immunotherapy. The heterogeneity of tumors and the dynamic nature of epithelial plasticity in cancer cells make it likely that targeting only 1 EMT-related process will be unsuccessful or only transiently successful. We suggest that with greater understanding of epithelial plasticity regulation, such as with the EMT, a more systematic targeting of multiple EMT regulatory networks will be the best path forward to improve cancer outcomes.

scholarly journals Targeting Heat Shock Protein 27 in Cancer: A Druggable Target for Cancer Treatment ?

2019 ◽  
Author(s):  
Seul-Ki Choi ◽  
Heejin Kam ◽  
Kye-Young Kim ◽  
Suk In Park ◽  
Yun-Sil Lee
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Cancer Treatment ◽  
Poor Prognosis ◽  
Treatment Resistance ◽  
Therapeutic Agents ◽  
Heat Shock Protein 27 ◽  
Cytoskeletal Remodeling ◽  
Protein Chaperone

Heat shock protein 27 (HSP27), induced by heat shock, environmental, and pathophysiological stressors, is a multi-dimensional protein that acts as a protein chaperone and an antioxidant. HSP27 plays a major role in the inhibition of apoptosis and actin cytoskeletal remodeling. HSP27 is upregulated in many cancers and is associated with poor prognosis, as well as treatment resistance whereby cells are protected from therapeutic agents that normally induce apoptosis. This review highlights the most recent findings and role of HSP27 in cancer, as well as strategies for using HSP27 inhibitors for therapeutic purposes.

Synthesis, characterization and anti-cancer applications of ytterbium doped gadolinium molybdate nanophosphor compound

2019 ◽  
Vol 9 (8) ◽  
pp. 882-894
Author(s):  
Jahnavi Rama Madhuri Kamaraju ◽  
Raghavendra Rao Kanchi ◽  
Rajesh Kumar Borra ◽  
Padma Suvarna Reniguntla ◽  
Satyanarayana Rentala
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Cancer Diagnosis ◽  
Breast Cancer Cells ◽  
Mri Contrast Agents ◽  
Gadolinium Complexes ◽  
Anti Cancer ◽  
Gadolinium Molybdate

Nanophosphor compounds with both diagnostic and therapeutic functions are potential for cancer diagnosis and treatment. Lanthanide complexes play a crucial role in cancer diagnosis and therapy. Gadolinium-complexes are commonly used as magnetic resonance imaging (MRI) contrast agents for cancer imaging. The role of a lanthanide, Ytterbium (Yb) in cancer treatment is not unknown. The present work focuses on finding the role of Yb when doped into Gadolinium complexes in cancer treatment. Our results demonstrate that Yb doped Gadolinium molybdate coated with biocompatible silica, effectively inhibited the viability of breast cancer cells after 24 and 48 h of treatment in in vitro, and in contrast the nanophosphor compounds did not affect the viability of healthy cells. Yb doped Gadolinium molybdate also up-regulated apoptotic genes in breast cancer cells. Hence we propose that Yb doped Gadolinium molybdate is a promising theranostic compound. To the best of our knowledge, this is the first report showing anti-cancer nature of Ytterbium-doped into Gadolinium nanophosphors.

miR-214 inhibits epithelial–mesenchymal transition of breast cancer cells via downregulation of RNF8

2019 ◽  
Vol 51 (8) ◽  
pp. 791-798 ◽  
Author(s):  
Lu Min ◽  
Chuanyang Liu ◽  
Jingyu Kuang ◽  
Xiaomin Wu ◽  
Lingyun Zhu
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Breast Cancer Metastasis ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition ◽  
Proliferation And Invasion

Abstract MicroRNAs (miRNAs) are a class of endogenous noncoding genes that regulate gene expression at the posttranscriptional level. In recent decades, miRNAs have been reported to play important roles in tumor growth and metastasis, while some reported functions of a specific miRNA in tumorigenesis are contradictory. In this study, we reevaluated the role of miR-214, which has been reported to serve as an oncogene or anti-oncogene in breast cancer metastasis. We found that miR-214 inhibited breast cancer via targeting RNF8, a newly identified regulator that could promote epithelial–mesenchymal transition (EMT). Specifically, the survival rate of breast cancer patients was positively correlated with miR-214 levels and negatively correlated with RNF8 expression. The overexpression of miR-214 inhibited cell proliferation and invasion of breast cancer, while suppression of miR-214 by chemically modified antagomir enhanced the proliferation and invasion of breast cancer cells. Furthermore, miR-214 could modulate the EMT process via downregulating RNF8. To our knowledge, this is the first report that reveals the role of the miR-214–RNF8 axis in EMT, and our results demonstrate a novel mechanism for miR-214 acting as a tumor suppressor through the regulation of EMT.

scholarly journals Cell to cell hijacking: Role of membrane nanotubes

2022 ◽  
Vol 13 (1) ◽  
pp. 1-2
Author(s):  
Karthikeyan Pethusamy ◽  
Ruby Dhar ◽  
Arun Kumar ◽  
Subhradip Karmakar
Keyword(s):  
Cancer Cells ◽  
Physiological Function ◽  
Cell Communication ◽  
Treatment Resistance ◽  
Cell Types ◽  
Chemotherapy Treatment ◽  
Tunneling Nanotubes ◽  
Membrane Nanotubes ◽  
Membrane Protrusions

Cell to Cell communications is the pivot for life processes. Any event that disrupts this leads to the loss of physiological function, eventually leading to cell death. Evolutionarily, cells developed an elaborate mechanism to undertake this paramount responsibility through cell surface glycocalyx, receptors, integrins, and other recognition molecules. Cells also exchange through local acting soluble mediators as well as through vesicles and exosomes. Recent development in this field led to the identification of a spectacular network of membrane process that seems to be the supremo of all that was known about cellular communications. These are called membrane nanotubes or tunneling nanotubes (TNT). Cellular communication can be subdivided into contact and contactless. The former provides more rapid and molecule transfer as compared to the latter. Tunneling nanotubes (TNTs) are a novel type of contact-based communication. TNTs are straight, thin membrane extensions connecting cells over long distances first reported in PC12 cells in 2004. TNT is believed to form from actin-based membrane protrusion. There are three different models of TNT formation. a>Protrusions from one cell grow and extend until it reaches the other cell, followed by a membrane fusion. b> Membrane protrusions grow from both cells until they meet and establish a connection c> TNT formation by cell dislodgement when cells migrate further apart from each other, and during this movement, TNT is formed. It is possible that all these three models may be operational depending on cell types and context. Tunneling nanotubes (TNT) are dynamic connections between cells, representing a novel route for cell-to-cell communication. TNT was reported in various cell types, like epithelial cells, neuronal cells, mesenchyma cells, and immune cells engaged in intercellular exchanges of molecules, subcellular organelles, and pathogen and viruses transport routes. TNT can extend up to 200 µm in length and about 50 nm to 1500 nm in diameter in macrophages. TNT can be established between similar cell types (homo-TNT) or between one cell type and another ( hetro TNT) and thus may be involved in the initiation and growth of cancer as well as dissemination of cancer cells. TNTs are also assumed to play a role in treatment resistance, e.g., in chemotherapy treatment of cancer. Recently, TNT has been used to hijack mitochondria from healthy cells by the cancer cells as a source of energy. TNT was also reported to transport miRNA and other RNA to the surrounding stroma creating an environment suitable for cancer growth. More research in this discipline is needed to understand the full function of these wonderful nanostructures.

scholarly journals ITPR3 Facilitates Tumor Growth, Metastasis and Stemness by Inducing the NF-ĸB/CD44 Pathway in Urinary Bladder Carcinoma

2020 ◽  
Author(s):  
Mengzhao Zhang ◽  
Lu Wang ◽  
Yangyang Yue ◽  
Lu Zhang ◽  
Tianjie Liu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Bladder Carcinoma ◽  
Cancer Metastasis ◽  
Critical Role ◽  
Cancer Tissue ◽  
Urinary Bladder Carcinoma ◽  
Mesenchymal Transition ◽  
Bladder Cancer Cells

Abstract Background: Bladder carcinoma is one of the most common urological cancers. ITPR3, as a ubiquitous endoplasmic reticulum calcium channel protein, was reported to be involved in the development and progression of various types of cancer. However, the potential roles and molecular mechanism of ITPR3 in bladder cancer are still unclear. Herein, we elucidated a novel role of ITPR3 in regulating the proliferation, metastasis, and stemness of bladder cancer cells.Methods: The expression of ITPR3 in bladder cancer was analyzed using public databases and bladder cancer tissue microarrays. To demonstrate the role of ITPR3 in regulating the NF-ĸB/CD44 pathway and the progression of bladder cancer, a series of molecular biology and biochemistry methods was performed on clinical tissues, along with in vivo and in vitro experiments. The methods used included western blot assay, quantitative RT-PCR assay, immunofluorescence assay, immunohistochemistry (IHC) assays, wound healing assay, Transwell assay, colony formation assay, tumorsphere formation assay, cell flow cytometry analysis, EdU assay, MTT assay, cell transfection, bisulfite sequencing PCR (BSP), a xenograft tumor model and a tail vein cancer metastasis model.Results: Higher ITPR3 expression was found in bladder cancer tissues and bladder cancer cells compared with the corresponding normal peritumor tissues and SV-HUC-1 cells, which was attributed to demethylation in the ITPR3 promoter region. ITPR3 promoted the proliferation of bladder cancer by accelerating cell cycle transformation and promoted local invasion and distant metastasis by inducing epithelial-to-mesenchymal transition (EMT). Meanwhile, ITPR3 maintained the cancer stemness phenotype by regulating CD44 expression. NF-κB, which is upstream of CD44, also played a critical role in this process.Conclusions: Our study clarifies that ITPR3 serves as an oncogene in bladder cancer cells and represents a novel candidate for bladder cancer diagnosis and treatment.

scholarly journals Nicaraven Attenuates Postoperative Systemic Inflammatory Responses-Induced Tumor Metastasis

2019 ◽  
Vol 27 (4) ◽  
pp. 1068-1074 ◽  
Author(s):  
Xu Zhang ◽  
Takahito Moriwaki ◽  
Tsuyoshi Kawabata ◽  
Shinji Goto ◽  
Ke-Xiang Liu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Tumor Metastasis ◽  
Intestinal Ischemia ◽  
Cancer Metastasis ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Inflammatory Cells ◽  
Major Surgery ◽  
Lewis Lung Cancer ◽  
Intestinal Ischemia Reperfusion

Abstract Background Inflammation has been demonstrated to promote cancer metastasis. Due to the well-known systemic inflammatory responses (SIR) after major surgery, it is critical to investigate and attenuate SIR-induced tumor metastasis of cancer patients suffering surgical procedures. Methods C57BL/6 mice were intravenously injected with Lewis lung cancer cells at 6, 24, and 72 h after the induction of intestinal ischemia/reperfusion (I/R) injury. We found that the number of tumor nodules significantly increased in lungs of mice injected with cancer cells at 6 h but not at 24 and 72 h after I/R injury. The administration of nicaraven 30 min before and 24 h after I/R injury effectively attenuated the enhanced tumor metastasis to lungs. Protein array showed the increase of various cytokines in plasma of mice at 6 h after I/R injury, but many of them were attenuated by the administration of nicaraven. Immunostaining indicated the increase of Ly6g-, CD206-, and CD11c-positive inflammatory cells in the lungs, but it was also attenuated by nicaraven administration. Conclusions Postoperative SIR-induced tumor metastasis have been clearly evidenced in our experimental model, and the administration of nicaraven may ameliorate the SIR-induced tumor metastasis by suppressing inflammatory responses.

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