scholarly journals Interaction of tumour cells with their microenvironment: ion channels and cell adhesion molecules. A focus on pancreatic cancer

2014 ◽  
Vol 369 (1638) ◽  
pp. 20130101 ◽  
Author(s):  
Annarosa Arcangeli ◽  
Olivia Crociani ◽  
Lapo Bencini
Keyword(s):  
Pancreatic Cancer ◽  
Ion Channels ◽  
Tumour Progression ◽  
Therapy Resistance ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Integrin Receptors ◽  
Strategic Position ◽  
Cellular Components

Cancer must be viewed as a ‘tissue’, constituted of both transformed cells and a heterogeneous microenvironment, the ‘tumour microenvironment’ (TME). The TME undergoes a complex remodelling during the course of multistep tumourigenesis, hence strongly contributing to tumour progression. Ion channels and transporters (ICTs), being expressed on both tumour cells and in the different cellular components of the TME, are in a strategic position to sense and mediate signals arising from the TME. Often, this transmission is mediated by integrin adhesion receptors, which are the main cellular receptors capable of mediating cell-to-cell and cell-to-matrix bidirectional signalling. Integrins can often operate in conjunction with ICT because they can behave as functional partners of ICT proteins. The role of integrin receptors in the crosstalk between tumour cells and the TME is particularly relevant in the context of pancreatic cancer (PC), characterized by an overwhelming TME which actively contributes to therapy resistance. We discuss the possibility that this occurs through integrins and ICTs, which could be exploited as targets to overcome chemoresistance in PC.

scholarly journals Ion channels in cancer: future perspectives and clinical potential

2014 ◽  
Vol 369 (1638) ◽  
pp. 20130108 ◽  
Author(s):  
Florian Lang ◽  
Christos Stournaras
Keyword(s):  
Ion Channels ◽  
Cell Survival ◽  
Tumour Cell ◽  
Tumour Growth ◽  
Therapeutic Potential ◽  
Short Review ◽  
Therapy Resistance ◽  
Tumour Cells ◽  
Anion Channels

Ion transport across the cell membrane mediated by channels and carriers participate in the regulation of tumour cell survival, death and motility. Moreover, the altered regulation of channels and carriers is part of neoplastic transformation. Experimental modification of channel and transporter activity impacts tumour cell survival, proliferation, malignant progression, invasive behaviour or therapy resistance of tumour cells. A wide variety of distinct Ca 2+ permeable channels, K + channels, Na + channels and anion channels have been implicated in tumour growth and metastasis. Further experimental information is, however, needed to define the specific role of individual channel isoforms critically important for malignancy. Compelling experimental evidence supports the assumption that the pharmacological inhibition of ion channels or their regulators may be attractive targets to counteract tumour growth, prevent metastasis and overcome therapy resistance of tumour cells. This short review discusses the role of Ca 2+ permeable channels, K + channels, Na + channels and anion channels in tumour growth and metastasis and the therapeutic potential of respective inhibitors.

scholarly journals 3D Cancer Models: Depicting Cellular Crosstalk within the Tumour Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4610
Author(s):  
Teresa Franchi-Mendes ◽  
Rodrigo Eduardo ◽  
Giacomo Domenici ◽  
Catarina Brito
Keyword(s):  
Tumour Progression ◽  
Critical Role ◽  
Cell Communication ◽  
Malignant Cell ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Precise Control ◽  
Cancer Models

The tumour microenvironment plays a critical role in tumour progression and drug resistance processes. Non-malignant cell players, such as fibroblasts, endothelial cells, immune cells and others, interact with each other and with the tumour cells, shaping the disease. Though the role of each cell type and cell communication mechanisms have been progressively studied, the complexity of this cellular network and its role in disease mechanism and therapeutic response are still being unveiled. Animal models have been mainly used, as they can represent systemic interactions and conditions, though they face recognized limitations in translational potential due to interspecies differences. In vitro 3D cancer models can surpass these limitations, by incorporating human cells, including patient-derived ones, and allowing a range of experimental designs with precise control of each tumour microenvironment element. We summarize the role of each tumour microenvironment component and review studies proposing 3D co-culture strategies of tumour cells and non-malignant cell components. Moreover, we discuss the potential of these modelling approaches to uncover potential therapeutic targets in the tumour microenvironment and assess therapeutic efficacy, current bottlenecks and perspectives.

Interactions of human monocytes with TMVs (tumour-derived microvesicles)

2013 ◽  
Vol 41 (1) ◽  
pp. 268-272 ◽  
Author(s):  
Monika Baj-Krzyworzeka ◽  
Jarosław Baran ◽  
Rafał Szatanek ◽  
Bożenna Mytar ◽  
Maciej Siedlar ◽  
...  
Keyword(s):  
Immune System ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Present Review ◽  
Human Monocytes ◽  
Cellular Components

The tumour microenvironment represents a dynamic complex milieu, which includes tumour cells, cells of the immune system and other (cellular and non-cellular) components. The role of these particular ‘puzzle pieces’ may change substantially due to their mutual interactions. The present review concerns different opinions on interactions that occur between monocytes, tumour cells and TMVs (tumour-derived microvesicles).

scholarly journals The Yin and Yang of tumour-derived extracellular vesicles in tumour immunity

2020 ◽  
Author(s):  
Takayoshi Yamauchi ◽  
Toshiro Moroishi
Keyword(s):  
Extracellular Vesicles ◽  
Tumour Progression ◽  
Tumour Microenvironment ◽  
Host Immunity ◽  
Biological Processes ◽  
Small Particles ◽  
Tumour Immunity ◽  
Heterogeneous Nature ◽  
Yin And Yang ◽  
Cellular Components

Abstract Extracellular vesicles (EVs) are small particles that are naturally released from various types of cells. EVs contain a wide variety of cellular components, such as proteins, nucleic acids, lipids and metabolites, which facilitate intercellular communication in diverse biological processes. In the tumour microenvironment, EVs have been shown to play important roles in tumour progression, including immune system–tumour interactions. Although previous studies have convincingly demonstrated the immunosuppressive functions of tumour-derived EVs, some studies have suggested that tumour-derived EVs can also stimulate host immunity, especially in therapeutic conditions. Recent studies have revealed the heterogeneous nature of EVs with different structural and biological characteristics that may account for the divergent functions of EVs in tumour immunity. In this review article, we provide a brief summary of our current understanding of tumour-derived EVs in immune activation and inhibition. We also highlight the emerging utility of EVs in the diagnosis and treatment of cancers and discuss the potential clinical applications of tumour-derived EVs.

scholarly journals Hypoxia and proangiogenic proteins in human ameloblastoma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Raíssa Pinheiro de Mendonça ◽  
Karolyny Martins Balbinot ◽  
Beatriz Voss Martins ◽  
Maria Sueli da Silva Kataoka ◽  
Ricardo Alves Mesquita ◽  
...  
Keyword(s):  
Aggressive Behaviour ◽  
Tumour Progression ◽  
Tumour Microenvironment ◽  
Odontogenic Cysts ◽  
Biological Behaviour ◽  
Odontogenic Tumours ◽  
Anti Vegf ◽  
The Mean

Abstract Ameloblastomas are epithelial odontogenic tumours that, although benign, are locally invasive and may exhibit aggressive behaviour. In the tumour microenvironment, the concentration of oxygen is reduced, which leads to intratumoral hypoxia. Under hypoxia, the crosstalk between the HIF-1α, MMP-2, VEGF, and VEGFR-2 proteins has been associated with hypoxia-induced angiogenesis, leading to tumour progression and increased invasiveness. This work showcases 24 ameloblastoma cases, 10 calcifying odontogenic cysts, and 9 dental follicles, used to investigate the expression of these proteins by immunohistochemistry. The anti-HIF-1α, anti-MMP-2, anti-VEGF, and anti-VEGFR-2 primary antibodies are used in this work. The results have been expressed by the mean grey value after immunostaining in images acquired with an objective of 40×. The ameloblastoma samples showed higher immunoexpression of HIF-1α, MMP-2, VEGF, and VEGFR-2 when compared to the dental follicles and calcifying odontogenic cysts. Ameloblastomas show a higher degree of expression of proteins associated with intratumoral hypoxia and proangiogenic proteins, which indicates the possible role of these proteins in the biological behaviour of this tumour.

scholarly journals Activation of blood coagulation in cancer: implications for tumour progression

2013 ◽  
Vol 33 (5) ◽  
Author(s):  
Luize G. Lima ◽  
Robson Q. Monteiro
Keyword(s):  
Blood Coagulation ◽  
Tumour Progression ◽  
Primary Tumour ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Protease Activated Receptors ◽  
Tumour Metastasis ◽  
Coagulation Proteins ◽  
Associated Proteins ◽  
Cancer Associated Thrombosis

Several studies have suggested a role for blood coagulation proteins in tumour progression. Herein, we discuss (1) the activation of the blood clotting cascade in the tumour microenvironment and its impact on primary tumour growth; (2) the intravascular activation of blood coagulation and its impact on tumour metastasis and cancer-associated thrombosis; and (3) antitumour therapies that target blood-coagulation-associated proteins. Expression levels of the clotting initiator protein TF (tissue factor) have been correlated with tumour cell aggressiveness. Simultaneous TF expression and PS (phosphatidylserine) exposure by tumour cells promote the extravascular activation of blood coagulation. The generation of blood coagulation enzymes in the tumour microenvironment may trigger the activation of PARs (protease-activated receptors). In particular, PAR1 and PAR2 have been associated with many aspects of tumour biology. The procoagulant activity of circulating tumour cells favours metastasis, whereas the release of TF-bearing MVs (microvesicles) into the circulation has been correlated with cancer-associated thrombosis. Given the role of coagulation proteins in tumour progression, it has been proposed that they could be targets for the development of new antitumour therapies.

scholarly journals ApoE-TREM2 axis induces pathogenic senescent-like myeloid cells in prostate cancer

2021 ◽  
Author(s):  
Arianna Calcinotto ◽  
Nicolò Bancaro ◽  
Martina Troiani ◽  
Rydell Arzola ◽  
Angela Rita Elia ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Histone Deacetylase Inhibitors ◽  
Tumour Progression ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
Treatment Resistance ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Mrna Levels ◽  
Immature Myeloid Cells

Abstract Tumour cells promote the expansion and intra-tumoural recruitment of Myeloid-derived suppressor cells (MDSCs), a subset of immature myeloid cells, that support tumour cell proliferation and confer treatment resistance. While immature myeloid cells have a very short lifespan, whether pathogenic MDSCs can persist in the tumour microenvironment remains unknown. Here, we report the identification of a subset of long-lasting MDSCs that upregulate markers of cellular senescence and the TREM2 receptor. Senescent-like MDSCs possess higher pro-inflammatory capabilities compared to canonical MDSCs. Genetic and pharmacological elimination of senescent-like MDSCs decreases tumour progression in different mouse models of prostate cancer. Mechanistically, we find that Apolipoprotein E (ApoE) secreted by prostate tumour cells binds TREM2 in senescent-like MDSCs, thereby regulating the survival of these cells. ApoE and TREM2 mRNA levels are upregulated in prostate cancers and correlate with poor patients’ prognosis. Taken together, these results reveal a novel mechanism by which the tumour microenvironment shapes the intra-tumoural immune response. Pathogenic senescent-like MDSCs persist longer in the tumour microenvironment and can be eliminated by histone deacetylase inhibitors enhancing the efficacy of standard therapy in prostate cancer.

scholarly journals The antimicrobial peptide Defensin cooperates with Tumour Necrosis Factor to drive tumour cell death in Drosophila

2019 ◽  
Author(s):  
Jean-Philippe Parvy ◽  
Yachuan Yu ◽  
Anna Dostalova ◽  
Shu Kondo ◽  
Alina Kurjan ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumour Necrosis Factor ◽  
Tumour Cell ◽  
Tumour Necrosis ◽  
Tumour Progression ◽  
Tumour Cells ◽  
Tumour Regression ◽  
Necrosis Factor

AbstractAntimicrobial peptides (AMPs) are small cationic molecules best known as mediators of the innate defence against microbial infection. While in vitro and ex vivo evidence suggest AMPs’ capacity to kill cancer cells, in vivo demonstration of an anti-tumour role of endogenous AMPs is lacking. Using a Drosophila model of tumourigenesis, we demonstrate a role for the AMP Defensin in the control of tumour progression. Our results reveal that Tumour Necrosis Factor mediates exposure of phosphatidylserine (PS), which makes tumour cells selectively sensitive to the action of Defensin remotely secreted from tracheal and fat tissues. Defensin binds tumour cells in PS-enriched areas, provoking cell death and tumour regression. Altogether, our results provide the first in vivo demonstration for a role of an endogenous AMP as an anti-cancer agent, as well as a mechanism that explains tumour cell sensitivity to the action of AMPs.

scholarly journals Cancer research using organoid technology

2020 ◽  
Author(s):  
Kai Kretzschmar
Keyword(s):  
Cancer Research ◽  
Tumour Microenvironment ◽  
Cancer Tissue ◽  
Cancer Genes ◽  
Mutational Signatures ◽  
Anti Cancer ◽  
Organoid Cultures ◽  
Tumour Initiation ◽  
Cellular Components

Abstract Organoid technology has rapidly transformed basic biomedical research and contributed to significant discoveries in the last decade. With the application of protocols to generate organoids from cancer tissue, organoid technology has opened up new opportunities for cancer research and therapy. Using organoid cultures derived from healthy tissues, different aspects of tumour initiation and progression are widely studied including the role of pathogens or specific cancer genes. Cancer organoid cultures, on the other hand, are applied to generate biobanks, perform drug screens, and study mutational signatures. With the incorporation of cellular components of the tumour microenvironment such as immune cells into the organoid cultures, the technology is now also exploited in the rapidly advancing field of immuno-oncology. In this review, I discuss how organoid technology is currently being utilised in cancer research and what obstacles are still to be overcome for its broader use in anti-cancer therapy.

Stem Cells in Tumour Microenvironment Aid in Prolonged Survival Rate of Cancer Cells and Developed Drug Resistance: Major Challenge in Osteosarcoma Treatment

2020 ◽  
Vol 21 (1) ◽  
pp. 44-52
Author(s):  
Bhaskar Birru ◽  
ChandraSai Potla Durthi ◽  
Santhosh Kacham ◽  
Madhuri Pola ◽  
Satish Babu Rajulapati ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Tumour Progression ◽  
Combined Treatment ◽  
Bone Cancer ◽  
Tumour Microenvironment ◽  
Surgical Removal ◽  
Therapeutic Approaches ◽  
Hypoxic Environment

Osteosarcoma is an aggressive bone cancer found in children and adolescents. The combined treatment strategy includes the surgical removal of tumour and subsequent chemotherapy to prevent the reoccurrence has been a widely accepted approach. However, the drug resistance developed by tumour cells causes recurrence of cancer. It is imperative to understand the molecular mechanism involved in the development of drug resistance and tumour progression for developing potential therapy. Tumour microenvironment and cellular cross-talk via activation of various signalling pathways are responsible for tumour progression and metastasis. The comprehensive reviews are already available on the tumour microenvironment, signalling cascades responsible for tumour progression, and cellular crosstalk between malignant cells and immune cells. Therefore, we intend to provide comprehend review postulating the importance of mesenchymal stem cells (MSCs) in osteosarcoma progression and metastasis. This paper is aimed to provide information sequentially includes: tumour microenvironment, MSCs role in osteosarcoma progression, the hypoxic environment in MSCs recruitment at the tumour site and the importance of exosomes in tumorigenesis, progression and metastasis. Overall, this review may enlighten the research on the role of MSCs and MSCs derived exosome in osteosarcoma progression and drug resistance. This possibly may result in developing novel therapeutic approaches to combat the osteosarcoma effectively and contributes for the development of prognosis tools for early diagnosis.

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