scholarly journals The Adhesome Network: Key Components Shaping the Tumour Stroma

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 525
Author(s):  
Pinelopi A. Nikolopoulou ◽  
Maria A. Koufaki ◽  
Vassiliki Kostourou
Keyword(s):  
Cancer Progression ◽  
Immune Cells ◽  
Cellular Responses ◽  
Tumour Microenvironment ◽  
Host Cells ◽  
Cancer Associated Fibroblasts ◽  
Tumour Stroma ◽  
Intracellular Protein ◽  
And Control

Beyond the conventional perception of solid tumours as mere masses of cancer cells, advanced cancer research focuses on the complex contributions of tumour-associated host cells that are known as “tumour microenvironment” (TME). It has been long appreciated that the tumour stroma, composed mainly of blood vessels, cancer-associated fibroblasts and immune cells, together with the extracellular matrix (ECM), define the tumour architecture and influence cancer cell properties. Besides soluble cues, that mediate the crosstalk between tumour and stroma cells, cell adhesion to ECM arises as a crucial determinant in cancer progression. In this review, we discuss how adhesome, the intracellular protein network formed at cell adhesions, regulate the TME and control malignancy. The role of adhesome extends beyond the physical attachment of cells to ECM and the regulation of cytoskeletal remodelling and acts as a signalling and mechanosensing hub, orchestrating cellular responses that shape the tumour milieu.

scholarly journals Cancer-Associated Fibroblasts in Oral Cancer: A Current Perspective on Function and Potential for Therapeutic Targeting

2021 ◽  
Vol 2 ◽  
Author(s):  
Kamila J. Bienkowska ◽  
Christopher J. Hanley ◽  
Gareth J. Thomas
Keyword(s):  
Oral Cancer ◽  
Cancer Progression ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Tumour Microenvironment ◽  
Cancer Associated Fibroblasts ◽  
Current Perspective ◽  
And Function ◽  
Exciting Development

The role of the tumour microenvironement (TME) in cancer progression and resistance to therapies is now widely recognized. The most prominent non-immune cell type in the microenvironment of oral cancer (OSCC) is cancer-associated fibroblasts (CAF). Although CAF are a poorly characterised and heterogenous cell population, those with an “activated” myofibroblastic phenotype have been shown to support OSCC progression, promoting growth, invasion and numerous other “hallmarks of malignancy.” CAF also confer broad resistance to different types of therapy, including chemo/radiotherapy and EGFR inhibitors; consistent with this, CAF-rich OSCC are associated with poor prognosis. In recent years, much CAF research has focused on their immunological role in the tumour microenvironment, showing that CAF shield tumours from immune attack through multiple mechanisms, and particularly on their role in promoting resistance to anti-PD-1/PD-L1 checkpoint inhibitors, an exciting development for the treatment of recurrent/metastatic oral cancer, but which fails in most patients. This review summarises our current understanding of CAF subtypes and function in OSCC and discusses the potential for targeting these cells therapeutically.

Cancer-associated stroma

2019 ◽  
pp. 303-313
Author(s):  
Wilma Mesker ◽  
Rob Tollenaar
Keyword(s):  
Immune Cells ◽  
Therapy Response ◽  
Tumour Microenvironment ◽  
Process Research ◽  
Cancer Drug ◽  
Cancer Growth ◽  
Tumour Stroma ◽  
Stromal Tissue ◽  
Patient Prognosis

Tumorigenesis is a dynamic process. Research on cancer development and metastases focuses on the tumour ‘host’ interface, and in particular on the role of the stromal tissue. For a few decades now, it has been well established that the tumour-associated stroma affects cancer growth and progression. Fibroblasts of the stroma orchestrate the recruitment of immune cells to promote cancer growth. Moreover, the tumour stroma of each tumour is different in terms of quantity and of cellular composition. The tumour stroma has gained interest in the clinic with regard to patient prognosis and its potential to influence therapy response. Where cancer drug development traditionally focused on targeting the tumour cells, emphasis has now shifted towards the tumour microenvironment for the development of novel therapeutics.

scholarly journals Targeting Metabolism in Cancer Cells and the Tumour Microenvironment for Cancer Therapy

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4831
Author(s):  
Jiaqi Li ◽  
Jie Qing Eu ◽  
Li Ren Kong ◽  
Lingzhi Wang ◽  
Yaw Chyn Lim ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Immune Cells ◽  
Therapeutic Strategy ◽  
Treatment Resistance ◽  
Tumour Microenvironment ◽  
Therapeutic Strategies ◽  
Metabolic Reprogramming ◽  
Cancer Associated Fibroblasts ◽  
Tumour Metabolism

Targeting altered tumour metabolism is an emerging therapeutic strategy for cancer treatment. The metabolic reprogramming that accompanies the development of malignancy creates targetable differences between cancer cells and normal cells, which may be exploited for therapy. There is also emerging evidence regarding the role of stromal components, creating an intricate metabolic network consisting of cancer cells, cancer-associated fibroblasts, endothelial cells, immune cells, and cancer stem cells. This metabolic rewiring and crosstalk with the tumour microenvironment play a key role in cell proliferation, metastasis, and the development of treatment resistance. In this review, we will discuss therapeutic opportunities, which arise from dysregulated metabolism and metabolic crosstalk, highlighting strategies that may aid in the precision targeting of altered tumour metabolism with a focus on combinatorial therapeutic strategies.

Cancer-associated stroma

2019 ◽  
pp. 303-313
Author(s):  
Wilma Mesker ◽  
Rob Tollenaar
Keyword(s):  
Immune Cells ◽  
Therapy Response ◽  
Tumour Microenvironment ◽  
Process Research ◽  
Cancer Drug ◽  
Cancer Growth ◽  
Tumour Stroma ◽  
Stromal Tissue ◽  
Patient Prognosis

Tumorigenesis is a dynamic process. Research on cancer development and metastases focuses on the tumour ‘host’ interface, and in particular on the role of the stromal tissue. For a few decades now, it has been well established that the tumour-associated stroma affects cancer growth and progression. Fibroblasts of the stroma orchestrate the recruitment of immune cells to promote cancer growth. Moreover, the tumour stroma of each tumour is different in terms of quantity and of cellular composition. The tumour stroma has gained interest in the clinic with regard to patient prognosis and its potential to influence therapy response. Where cancer drug development traditionally focused on targeting the tumour cells, emphasis has now shifted towards the tumour microenvironment for the development of novel therapeutics.

scholarly journals The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1239
Author(s):  
Leila Jahangiri ◽  
Tala Ishola ◽  
Perla Pucci ◽  
Ricky M. Trigg ◽  
Joao Pereira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Regulatory Networks ◽  
Epithelial To Mesenchymal Transition ◽  
Tumour Microenvironment ◽  
Repair Capacity ◽  
Mesenchymal Transition ◽  
Cellular Processes

Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.

The Role of Cancer-associated Fibroblasts in Tumorigenesis of Gastric Cancer

2018 ◽  
Vol 24 (28) ◽  
pp. 3297-3302 ◽  
Author(s):  
Zhilong Ma ◽  
Min Chen ◽  
Xiaohu Yang ◽  
Bin Xu ◽  
Zhenshun Song ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Tumor Biology ◽  
Vital Role ◽  
Cancer Associated Fibroblasts ◽  
Gastric Cancer Cells ◽  
Stromal Fibroblasts ◽  
Tumor Microenvironments ◽  
Tumorigenesis And Progression

Cancer-associated fibroblasts (CAFs) are an important cell type present in solid tumor microenvironments, including that of gastric cancer. They play a vital role in the promotion of tumorigenesis, angiogenesis, and cancer progression through paracrine signaling and modulation of the extracellular matrix. However, the exact molecular mechanism underlying the interaction between gastric cancer cells and stromal fibroblasts remains poorly understood. Recent studies have demonstrated that various factors, such as gene and microRNA variations, are involved in this process. This review discusses recent advances in understanding how these factors are regulated in CAFs and how they affect tumor biology, which may improve our understanding of their role in gastric cancer tumorigenesis and progression and provide new promising targets for therapeutic strategies.

scholarly journals Correlation Between Immune Lymphoid Cells and Plasmacytoid Dendritic Cells in Human Colon Cancer

2020 ◽  
Author(s):  
Jing Wu ◽  
Hang Cheng ◽  
Tete Li ◽  
Helei Wang ◽  
Guoxia Zang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Dendritic Cells ◽  
Rna Sequencing ◽  
Immune Cells ◽  
Human Colon ◽  
Tumour Microenvironment ◽  
Plasmacytoid Dendritic Cells ◽  
Lymphoid Cells ◽  
Human Colon Cancer

Abstract Background: Innate lymphoid cells (ILCs), so far studied mostly in mouse models, are important tissue-resident innate immune cells that play important roles in the colorectal cancer microenvironment and maintain the mucosal tissue homeostasis. Plasmacytoid dendritic cells (pDCs) present complexity in various tumour types and are correlated with poor prognosis. pDCs can promote HIV-1–induced group 3 ILC (ILC3) depletion through the CD95 pathway. However, the role of ILC3s in human colon cancer and their correlation with other immune cells, especially pDCs, remain unclear. Methods: We characterised ILCs and pDCs in the tumour microenvironment of 58 colon cancer patients by flow cytometry and selected three patients for RNA sequencing. Results: ILC3s were negatively correlated, and pDCs were positively correlated, with cancer pathological grade. There was a negative correlation between the numbers of ILC3s and pDCs in tumour tissues. RNA sequencing confirmed the correlations between ILC3s and pDCs and highlighted the potential function of many ILC- and pDC-associated differentially expressed genes in the regulation of tumour immunity. pDCs can induce apoptosis of ILC3s through the CD95 pathway in the tumour microenvironment. Conclusions: One of the interactions between ILC3s and pDCs is via the CD95 pathway, which may help explain the role of ILC3s in colon cancer.

scholarly journals MicroRNAs in the tumour microenvironment: big role for small players

2013 ◽  
Vol 20 (5) ◽  
pp. R257-R267 ◽  
Author(s):  
Patsy Soon ◽  
Hippokratis Kiaris
Keyword(s):  
Clinical Characteristics ◽  
Experimental Studies ◽  
Anticancer Therapy ◽  
Tumour Microenvironment ◽  
Regulatory Role ◽  
Tumour Stroma ◽  
Physiological Processes ◽  
Non Coding Rnas

MicroRNAs (miRNAs) represent a class of small non-coding RNAs with an important regulatory role in various physiological processes as well as in several pathologies including cancers. It is noteworthy that recent evidence suggests that the regulatory role of miRNAs during carcinogenesis is not limited to the cancer cells but they are also implicated in the activation of tumour stroma and its transition into a cancer-associated state. Results from experimental studies involving cells culturedin vitroand mice bearing experimental tumours, corroborated by profiling of clinical cancers for miRNA expression, underline this role and identify miRNAs as a potent regulator of the crosstalk between cancer and stroma cells. Considering the fundamental role of the tumour microenvironment in determining both the clinical characteristics of the disease and the efficacy of anticancer therapy, miRNAs emerge as an attractive target bearing important prognostic and therapeutic significance during carcinogenesis. In this article, we will review the available results that underline the role of miRNAs in tumour stroma biology and emphasise their potential value as tools for the management of the disease.

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