scholarly journals Impact of the Tumor Microenvironment on Tumor Heterogeneity and Consequences for Cancer Cell Plasticity and Stemness

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3716
Author(s):  
Ralf Hass ◽  
Juliane von der Ohe ◽  
Hendrik Ungefroren
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cell ◽  
Tumor Heterogeneity ◽  
Cancer Therapies ◽  
Epigenetic Alterations ◽  
Cell Plasticity ◽  
Cellular Phenotypes ◽  
Therapy Success ◽  
Physical And Chemical

Tumor heterogeneity is considered the major cause of treatment failure in current cancer therapies. This feature of solid tumors is not only the result of clonal outgrowth of cells with genetic mutations, but also of epigenetic alterations induced by physical and chemical signals from the tumor microenvironment (TME). Besides fibroblasts, endothelial and immune cells, mesenchymal stroma/stem-like cells (MSCs) and tumor-associated macrophages (TAMs) intimately crosstalk with cancer cells and can exhibit both anti- and pro-tumorigenic effects. MSCs can alter cancer cellular phenotypes to increase cancer cell plasticity, eventually resulting in the generation of cancer stem cells (CSCs). The shift between different phenotypic states (phenotype switching) of CSCs is controlled via both genetic programs, such as epithelial-mesenchymal transdifferentiation or retrodifferentiation, and epigenetic alterations triggered by signals from the TME, like hypoxia, spatial heterogeneity or stromal cell-derived chemokines. Finally, we highlight the role of spontaneous cancer cell fusion with various types of stromal cells. i.e., MSCs in shaping CSC plasticity. A better understanding of cell plasticity and phenotype shifting in CSCs is a prerequisite for exploiting this phenomenon to reduce tumor heterogeneity, thereby improving the chance for therapy success.

scholarly journals The Role of Herbal Bioactive Components in Mitochondria Function and Cancer Therapy

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Fangfang Tao ◽  
Yanrong Zhang ◽  
Zhiqian Zhang
Keyword(s):  
Cancer Therapy ◽  
Cancer Cell ◽  
Apoptotic Cell ◽  
Redox Status ◽  
Cancer Therapies ◽  
Bioactive Components ◽  
Atp Production

Mitochondria are highly dynamic double-membrane organelles which play a well-recognized role in ATP production, calcium homeostasis, oxidation-reduction (redox) status, apoptotic cell death, and inflammation. Dysfunction of mitochondria has long been observed in a number of human diseases, including cancer. Targeting mitochondria metabolism in tumors as a cancer therapeutic strategy has attracted much attention for researchers in recent years due to the essential role of mitochondria in cancer cell growth, apoptosis, and progression. On the other hand, a series of studies have indicated that traditional medicinal herbs, including traditional Chinese medicines (TCM), exert their potential anticancer effects as an effective adjunct treatment for alleviating the systemic side effects of conventional cancer therapies, for reducing the risk of recurrence and cancer mortality and for improving the quality of patients’ life. An amazing feature of these structurally diverse bioactive components is that majority of them target mitochondria to provoke cancer cell-specific death program. The aim of this review is to summarize the in vitro and in vivo studies about the role of these herbs, especially their bioactive compounds in the modulation of the disturbed mitochondrial function for cancer therapy.

scholarly journals Single-cell tumor-immune microenvironment of BRCA1/2 mutated high-grade serous ovarian cancer

2021 ◽  
Author(s):  
Inga-Maria Launonen ◽  
Nuppu Lyytikäinen ◽  
Julia Casado ◽  
Ella Anttila ◽  
Angéla Szabó ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Single Cell ◽  
Single Cells ◽  
High Grade ◽  
Prognostic Role ◽  
Immune Microenvironment ◽  
Proteomic Data ◽  
Tumor Immune Microenvironment ◽  
Cellular Phenotypes

Abstract The majority of high-grade serous ovarian cancers (HGSCs) are deficient in homologous recombination (HR) DNA repair, most commonly due to mutations or hypermethylation of the BRCA1/2 genes. We aimed to discover how BRCA1/2 mutations shape the cellular phenotypes and spatial interactions of the tumor microenvironment. Using a highly multiplex immunofluorescence and image analysis we generated spatial proteomic data for 21 markers in 124,623 single cells from 112 tumor cores originating from 31 tumors with BRCA1/2 mutation (BRCA1/2mut), and from 13 tumors without alterations in HR genes (HRwt). We identified a phenotypically distinct tumor microenvironment in the BRCA1/2mut tumors with evidence of increased immunosurveillance. Importantly, we found an opposing prognostic role of a proliferative tumor-cell phenotypic subpopulation in the HR-genotypes, which associated with enhanced spatial tumor-immune interactions by the CD8+ and CD4+T-cells in BRCA1/2mut tumors. The single-cell spatial landscapes indicate distinct patterns of spatial immunosurveillance with the premise to improve immunotherapeutic strategies and patient stratification in HGSC.

Abstract 2538: The emerging role of SOX2 in cancer cell plasticity and EGFR-TKI resistance

2016 ◽  
Author(s):  
Yu-Fan Chiu ◽  
Ming-Han Kuo ◽  
An-Chun Lee ◽  
Yu-Ting Chou
Keyword(s):  
Cancer Cell ◽  
Cell Plasticity ◽  
Tki Resistance ◽  
Egfr Tki

scholarly journals Complement and Cancer—A Dysfunctional Relationship?

Antibodies ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 61
Author(s):  
Joshua M. Thurman ◽  
Jennifer Laskowski ◽  
Raphael A. Nemenoff
Keyword(s):  
Tumor Microenvironment ◽  
Complement Activation ◽  
Tumor Biology ◽  
Clinical Work ◽  
The Body ◽  
Great Promise ◽  
Cancer Therapies ◽  
Complement Inhibitors ◽  
Cell Immunity

Although it was long believed that the complement system helps the body to identify and remove transformed cells, it is now clear that complement activation contributes to carcinogenesis and can also help tumors to escape immune-elimination. Complement is activated by several different mechanisms in various types of cancer, and complement activation fragments have multiple different downstream effects on cancer cells and throughout the tumor microenvironment. Thus, the role of complement activation in tumor biology may vary among different types of cancer and over time within a single tumor. In multiple different pre-clinical models, however, complement activation has been shown to recruit immunosuppressive myeloid cells into the tumor microenvironment. These cells, in turn, suppress anti-tumor T cell immunity, enabling the tumor to grow. Based on extensive pre-clinical work, therapeutic complement inhibitors hold great promise as a new class of immunotherapy. A greater understanding of the role of complement in tumor biology will improve our ability to identify those patients most likely to benefit from this treatment and to rationally combine complement inhibitors with other cancer therapies.

scholarly journals Commutators of PAR-1 signaling in cancer cell invasion reveal an essential role of the Rho–Rho kinase axis and tumor microenvironment

Oncogene ◽  
2005 ◽  
Vol 24 (56) ◽  
pp. 8240-8251 ◽  
Author(s):  
Quang-Dé Nguyen ◽  
Olivier De Wever ◽  
Erik Bruyneel ◽  
An Hendrix ◽  
Wan-Zhuo Xie ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Essential Role ◽  
Rho Kinase ◽  
Cancer Cell Invasion

scholarly journals Tumorigenic Cell Reprogramming and Cancer Plasticity: Interplay between Signaling, Microenvironment, and Epigenetics

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Vittoria Poli ◽  
Luca Fagnocchi ◽  
Alessio Zippo
Keyword(s):  
Cancer Cell ◽  
Tumor Heterogeneity ◽  
Critical Role ◽  
Cell Reprogramming ◽  
Tumor Initiation ◽  
Cell Of Origin ◽  
Cell Plasticity ◽  
New Developments ◽  
Dynamic Mechanisms ◽  
Tumor Maintenance

Accumulating evidences indicate that many tumors rely on subpopulations of cancer stem cells (CSCs) with the ability to propagate malignant clones indefinitely and to produce an overt cancer. Of importance, CSCs seem to be more resistant to the conventional cytotoxic treatments, driving tumor growth and contributing to relapse. CSCs can originate from normal committed cells which undergo tumor-reprogramming processes and reacquire a stem cell-like phenotype. Increasing evidences also show how tumor homeostasis and progression strongly rely on the capacity of nontumorigenic cancer cells to dedifferentiate to CSCs. Both tumor microenvironment and epigenetic reprogramming drive such dynamic mechanisms, favoring cancer cell plasticity and tumor heterogeneity. Here, we report new developments which led to an advancement in the CSC field, elucidating the concepts of cancer cell of origin and CSC plasticity in solid tumor initiation and maintenance. We further discuss the main signaling pathways which, under the influence of extrinsic environmental factors, play a critical role in the formation and maintenance of CSCs. Moreover, we propose a review of the main epigenetic mechanisms whose deregulation can favor the onset of CSC features both in tumor initiation and tumor maintenance. Finally, we provide an update of the main strategies that could be applied to target CSCs and cancer cell plasticity.

scholarly journals Role of Exosomic MicroRNAs in Cancer Cell Cross‐Talk within the Tumor Microenvironment

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Muller Fabbri ◽  
Petra Wise ◽  
Mariam Murtadha ◽  
Paolo Neviani ◽  
Kishore Challagundla
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cell ◽  
Cross Talk

scholarly journals Application of Single-Cell Multi-Omics in Dissecting Cancer Cell Plasticity and Tumor Heterogeneity

2021 ◽  
Vol 8 ◽  
Author(s):  
Deshen Pan ◽  
Deshui Jia
Keyword(s):  
Single Cell ◽  
Cancer Cell ◽  
Tumor Heterogeneity ◽  
Recent Progress ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Tumor Development ◽  
Cell Plasticity ◽  
Translational Cancer Research ◽  
Cellular Components

Tumor heterogeneity, a hallmark of cancer, impairs the efficacy of cancer therapy and drives tumor progression. Exploring inter- and intra-tumoral heterogeneity not only provides insights into tumor development and progression, but also guides the design of personalized therapies. Previously, high-throughput sequencing techniques have been used to investigate the heterogeneity of tumor ecosystems. However, they could not provide a high-resolution landscape of cellular components in tumor ecosystem. Recently, advance in single-cell technologies has provided an unprecedented resolution to uncover the intra-tumoral heterogeneity by profiling the transcriptomes, genomes, proteomes and epigenomes of the cellular components and also their spatial distribution, which greatly accelerated the process of basic and translational cancer research. Importantly, it has been demonstrated that some cancer cells are able to transit between different states in order to adapt to the changing tumor microenvironment, which led to increased cellular plasticity and tumor heterogeneity. Understanding the molecular mechanisms driving cancer cell plasticity is critical for developing precision therapies. In this review, we summarize the recent progress in dissecting the cancer cell plasticity and tumor heterogeneity by use of single-cell multi-omics techniques.

scholarly journals Endothelial YAP/TAZ Signaling in Angiogenesis and Tumor Vasculature

2021 ◽  
Vol 10 ◽  
Author(s):  
Aukie Hooglugt ◽  
Miesje M. van der Stoel ◽  
Reinier A. Boon ◽  
Stephan Huveneers
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Metastasis ◽  
Lymphatic Vessels ◽  
Cancer Therapies ◽  
Tumor Cell Growth ◽  
Vascular Normalization ◽  
Cancer Treatments ◽  
Anti Cancer ◽  
Tumor Endothelium

Solid tumors are dependent on vascularization for their growth. The hypoxic, stiff, and pro-angiogenic tumor microenvironment induces angiogenesis, giving rise to an immature, proliferative, and permeable vasculature. The tumor vessels promote tumor metastasis and complicate delivery of anti-cancer therapies. In many types of tumors, YAP/TAZ activation is correlated with increased levels of angiogenesis. In addition, endothelial YAP/TAZ activation is important for the formation of new blood and lymphatic vessels during development. Oncogenic activation of YAP/TAZ in tumor cell growth and invasion has been studied in great detail, however the role of YAP/TAZ within the tumor endothelium remains insufficiently understood, which complicates therapeutic strategies aimed at targeting YAP/TAZ in cancer. Here, we overview the upstream signals from the tumor microenvironment that control endothelial YAP/TAZ activation and explore the role of their downstream targets in driving tumor angiogenesis. We further discuss the potential for anti-cancer treatments and vascular normalization strategies to improve tumor therapies.

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