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.

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 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 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.

scholarly journals The role of the tumour microenvironment in the angiogenesis of pituitary tumours

Endocrine ◽  
2020 ◽  
Vol 70 (3) ◽  
pp. 593-606
Author(s):  
Pedro Marques ◽  
Sayka Barry ◽  
Eivind Carlsen ◽  
David Collier ◽  
Amy Ronaldson ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Immune Cells ◽  
Microvessel Density ◽  
Tumour Microenvironment ◽  
Vascular Morphology ◽  
Hla Dr ◽  
M1 Macrophage ◽  
Culture Supernatants

Abstract Purpose Angiogenesis has been studied in pituitary neuroendocrine tumours (PitNETs), but the role of the tumour microenvironment (TME) in regulating PitNET angiogenesis remains unknown. We aimed to characterise the role of TME components in determining the angiogenetic PitNET profile, focusing on immune cells and tumour-derived cytokines. Methods Immune cells were studied by immunohistochemistry in 24 human PitNETs (16 non-functioning-PitNETs (NF-PitNETs) and 8 somatotrophinomas): macrophages (CD68, CD163, HLA-DR), cytotoxic (CD8) and T helper (CD4) lymphocytes, regulatory T cells (FOXP3), B cells (CD20) and neutrophils (neutrophil elastase); endothelial cells were assessed with CD31. Five normal pituitaries (NP) were included for comparison. Microvessel density and vascular morphology were estimated with ImageJ. The cytokine secretome from these PitNETs were assessed on culture supernatants using a multiplex immunoassay panel. Results Microvessel density/area was higher in NP than PitNETs, which also had rounder and more regular vessels. NF-PitNETs had vessels of increased calibre compared to somatotrophinomas. The M2:M1 macrophage ratio correlated with microvessel area. PitNETs with more CD4+ T cells had higher microvessel area, while tumours with more FOXP3+ cells were associated with lower microvessel density. PitNETs with more B cells had rounder vessels. Of the 42 PitNET-derived cytokines studied, CCL2, CXCL10 and CX3CL1 correlated with microvessel density and vessel architecture parameters. Conclusions M2 macrophages appear to play a role in PitNET neovascularisation, while B, CD4+ and FOXP3+ lymphocytes, as well as non-cellular TME elements such as CCL2, CXCL10 and CX3CL1, may also modulate the angiogenesis of PitNETs.

Analysis of the intricate relationship between chronic inflammation and cancer

2015 ◽  
Vol 468 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Edna Zhi Pei Chai ◽  
Kodappully Sivaraman Siveen ◽  
Muthu K. Shanmugam ◽  
Frank Arfuso ◽  
Gautam Sethi
Keyword(s):  
Chronic Inflammation ◽  
Immune Cells ◽  
Patient Management ◽  
Critical Role ◽  
Tumour Microenvironment ◽  
Therapeutic Strategies ◽  
Exponential Rate ◽  
Hereditary Factors ◽  
Tumour Initiation

Deregulated inflammatory response plays a pivotal role in the initiation, development and progression of tumours. Potential molecular mechanism(s) that drive the establishment of an inflammatory-tumour microenvironment is not entirely understood owing to the complex cross-talk between pro-inflammatory and tumorigenic mediators such as cytokines, chemokines, oncogenes, enzymes, transcription factors and immune cells. These molecular mediators are critical linchpins between inflammation and cancer, and their activation and/or deactivation are influenced by both extrinsic (i.e. environmental and lifestyle) and intrinsic (i.e. hereditary) factors. At present, the research pertaining to inflammation-associated cancers is accumulating at an exponential rate. Interest stems from hope that new therapeutic strategies against molecular mediators can be identified to assist in cancer treatment and patient management. The present review outlines the various molecular and cellular inflammatory mediators responsible for tumour initiation, progression and development, and discusses the critical role of chronic inflammation in tumorigenesis.

scholarly journals Immune Cells in Cancer Therapy and Drug Delivery

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Ceren Eyileten ◽  
Kinga Majchrzak ◽  
Zofia Pilch ◽  
Katarzyna Tonecka ◽  
Joanna Mucha ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cell Proliferation ◽  
T Cells ◽  
Dendritic Cells ◽  
Immune Cells ◽  
Critical Role ◽  
Tumour Microenvironment ◽  
Cytokines And Chemokines

Recent studies indicate the critical role of tumour associated macrophages, tumour associated neutrophils, dendritic cells, T lymphocytes, and natural killer cells in tumourigenesis. These cells can have a significant impact on the tumour microenvironment via their production of cytokines and chemokines. Additionally, products secreted from all these cells have defined specific roles in regulating tumour cell proliferation, angiogenesis, and metastasis. They act in a protumour capacityin vivoas evidenced by the recent studies indicating that macrophages, T cells, and neutrophils may be manipulated to exhibit cytotoxic activity against tumours. Therefore therapy targeting these cells may be promising, or they may constitute drug or anticancer particles delivery systems to the tumours. Herein, we discussed all these possibilities that may be used in cancer treatment.

scholarly journals Acidic and Hypoxic Microenvironment in Melanoma: Impact of Tumour Exosomes on Disease Progression

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3311
Author(s):  
Zaira Boussadia ◽  
Adriana Rosa Gambardella ◽  
Fabrizio Mattei ◽  
Isabella Parolini
Keyword(s):  
Malignant Melanoma ◽  
Immune Cells ◽  
Stromal Cells ◽  
Immune Surveillance ◽  
Tumour Microenvironment ◽  
Response To Treatment ◽  
Malignant Phenotype ◽  
Hypoxic Conditions ◽  
Melanoma Diagnosis

The mechanisms of melanoma progression have been extensively studied in the last decade, and despite the diagnostic and therapeutic advancements pursued, malignant melanoma still accounts for 60% of skin cancer deaths. Therefore, research efforts are required to better define the intercellular molecular steps underlying the melanoma development. In an attempt to represent the complexity of the tumour microenvironment (TME), here we analysed the studies on melanoma in acidic and hypoxic microenvironments and the interactions with stromal and immune cells. Within TME, acidity and hypoxia force melanoma cells to adapt and to evolve into a malignant phenotype, through the cooperation of the tumour-surrounding stromal cells and the escape from the immune surveillance. The role of tumour exosomes in the intercellular crosstalk has been generally addressed, but less studied in acidic and hypoxic conditions. Thus, this review aims to summarize the role of acidic and hypoxic microenvironment in melanoma biology, as well as the role played by melanoma-derived exosomes (Mexo) under these conditions. We also present a perspective on the characteristics of acidic and hypoxic exosomes to disclose molecules, to be further considered as promising biomarkers for an early detection of the disease. An update on the use of exosomes in melanoma diagnosis, prognosis and response to treatment will be also provided and discussed.

scholarly journals Extracellular citrate and metabolic adaptations of cancer cells

2021 ◽  
Author(s):  
E. Kenneth Parkinson ◽  
Jerzy Adamski ◽  
Grit Zahn ◽  
Andreas Gaumann ◽  
Fabian Flores-Borja ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Cancer Cells ◽  
Immune Cells ◽  
Warburg Effect ◽  
Cancer Metabolism ◽  
Krebs Cycle ◽  
Therapy Resistance ◽  
Tumour Microenvironment ◽  
The Warburg Effect

Abstract It is well established that cancer cells acquire energy via the Warburg effect and oxidative phosphorylation. Citrate is considered to play a crucial role in cancer metabolism by virtue of its production in the reverse Krebs cycle from glutamine. Here, we review the evidence that extracellular citrate is one of the key metabolites of the metabolic pathways present in cancer cells. We review the different mechanisms by which pathways involved in keeping redox balance respond to the need of intracellular citrate synthesis under different extracellular metabolic conditions. In this context, we further discuss the hypothesis that extracellular citrate plays a role in switching between oxidative phosphorylation and the Warburg effect while citrate uptake enhances metastatic activities and therapy resistance. We also present the possibility that organs rich in citrate such as the liver, brain and bones might form a perfect niche for the secondary tumour growth and improve survival of colonising cancer cells. Consistently, metabolic support provided by cancer-associated and senescent cells is also discussed. Finally, we highlight evidence on the role of citrate on immune cells and its potential to modulate the biological functions of pro- and anti-tumour immune cells in the tumour microenvironment. Collectively, we review intriguing evidence supporting the potential role of extracellular citrate in the regulation of the overall cancer metabolism and metastatic activity.

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