The emergence of solid stress as a potent biomechanical marker of tumour progression

2018 ◽  
Vol 2 (5) ◽  
pp. 739-749
Author(s):  
Alain Vella ◽  
Enanga M. Eko ◽  
Armando del Río Hernández
Keyword(s):  
Stromal Cells ◽  
Tumour Growth ◽  
Tumour Progression ◽  
Tissue Structure ◽  
Signalling Pathways ◽  
Matrix Stiffness ◽  
Cell Behaviour ◽  
Solid Stress ◽  
Comprehensive Knowledge ◽  
Macro Scale

Cancer is a disease of dysregulated mechanics which alters cell behaviour, compromises tissue structure, and promotes tumour growth and metastasis. In the context of tumour progression, the most widely studied of biomechanical markers is matrix stiffness as tumour tissue is typically stiffer than healthy tissue. However, solid stress has recently been identified as another marker of tumour growth, with findings strongly suggesting that its role in cancer is distinct from that of stiffness. Owing to the relative infancy of the field which draws from diverse disciplines, a comprehensive knowledge of the relationships between solid stress, tumorigenesis, and metastasis is likely to provide new and valuable insights. In this review, we discuss the micro- and macro-scale biomechanical interactions that give rise to solid stresses, and also examine the techniques developed to quantify solid stress within the tumour environment. Moreover, by reviewing the effects of solid stress on tissues, cancer and stromal cells, and signalling pathways, we also detail its mode of action at each level of the cancer cascade.

Ethanolic Extract of Algerian Propolis and Galangin Decreased Murine Melanoma Tumor Progression in Mice

2016 ◽  
Vol 16 (9) ◽  
pp. 1172-1183 ◽  
Author(s):  
Lamia Benguedouar ◽  
Mesbah Lahouel ◽  
Sophie C. Gangloff ◽  
Anne Durlach ◽  
Florent Grange ◽  
...  
Keyword(s):  
Tumour Growth ◽  
Tumour Progression ◽  
Ethanolic Extract ◽  
Complementary Therapy ◽  
Melanoma Cells ◽  
Biological Properties ◽  
Therapeutic Treatment ◽  
Melanoma Tumor ◽  
Ki 67

Melanoma is the more dangerous skin cancer, and metastatic melanoma still carries poor prognosis. Despite recent therapeutic advances, prolonged survival remains rare and research is still required. Propolis extracts from many countries have attracted a great deal of attention for their biological properties. We here investigated the ability of an ethanolic extract of Algerian propolis (EEP) to control melanoma tumour growth when given to mice bearing B16F1melanoma tumour either as preventive or as therapeutic treatment. EEP given after tumour occurrence increased mice survival (+30%) and reduced tumour growth (-75%). This was associated with a decrease of the Mitotic Index (-75%) and of Ki-67 (-50%) expression. When given either before or both before and after tumour occurrence, EEP reduced tumour growth but without prolonging mice life. Isolation of B16F1 melanoma cells from resected tumour showed that preventive and curative EEP treatments reduced invasiveness by 55% and 40% respectively compared to control. Galangin, one of the most abundant flavonoids in propolis, significantly reduced the number of melanoma cells in vitro and induced autophagy/apoptosis dose dependently. In conclusion, we showed that EEP reduced melanoma tumour progression/dissemination and could extend mice lifespan when used as therapeutic treatment. Then, EEP may help patients with melanoma when used as a complementary therapy to classical treatment for which autophagy is not contraindicated.

scholarly journals Crosstalk between cancer cells and blood endothelial and lymphatic endothelial cells in tumour and organ microenvironment

2015 ◽  
Vol 17 ◽  
Author(s):  
Esak Lee ◽  
Niranjan B. Pandey ◽  
Aleksander S. Popel
Keyword(s):  
Endothelial Cells ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Tumour Growth ◽  
Tumour Progression ◽  
Lymphatic Vessels ◽  
Cell Types ◽  
Malignant Cell ◽  
Lymphatic Endothelial Cells ◽  
Tumour Blood

Tumour and organ microenvironments are crucial for cancer progression and metastasis. Crosstalk between multiple non-malignant cell types in the microenvironments and cancer cells promotes tumour growth and metastasis. Blood and lymphatic endothelial cells (BEC and LEC) are two of the components in the microenvironments. Tumour blood vessels (BV), comprising BEC, serve as conduits for blood supply into the tumour, and are important for tumour growth as well as haematogenous tumour dissemination. Lymphatic vessels (LV), comprising LEC, which are relatively leaky compared with BV, are essential for lymphogenous tumour dissemination. In addition to describing the conventional roles of the BV and LV, we also discuss newly emerging roles of these endothelial cells: their crosstalk with cancer cells via molecules secreted by the BEC and LEC (also called angiocrine and lymphangiocrine factors). This review suggests that BEC and LEC in various microenvironments can be orchestrators of tumour progression and proposes new mechanism-based strategies to discover new therapies to supplement conventional anti-angiogenic and anti-lymphangiogenic therapies.

scholarly journals Cytokine Patterns in Brain Tumour Progression

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Radu Albulescu ◽  
Elena Codrici ◽  
Ionela Daniela Popescu ◽  
Simona Mihai ◽  
Laura Georgiana Necula ◽  
...  
Keyword(s):  
Immune System ◽  
Inflammatory Cytokines ◽  
Tumour Growth ◽  
Tumour Progression ◽  
Inflammatory Cells ◽  
Serum Levels ◽  
Angiogenic Factors ◽  
System Response ◽  
Gm Csf ◽  
Immune System Response

Inflammation represents the immune system response to external or internal aggressors such as injury or infection in certain tissues. The body’s response to cancer has many parallels with inflammation and repair; the inflammatory cells and cytokines present in tumours are more likely to contribute to tumour growth, progression, and immunosuppression, rather than in building an effective antitumour defence. Using new proteomic technology, we have investigated serum profile of pro- (IL-1β, IL-6, IL-8, IL-12, GM-CSF, and TNF-α) and anti-inflammatory cytokines (IL-4, IL-10), along with angiogenic factors (VEGF, bFGF) in order to assess tumoural aggressiveness. Our results indicate significant dysregulation in serum levels of cytokines and angiogenic factors, with over threefold upregulation of IL-6, IL-1β, TNF-α, and IL-10 and up to twofold upregulation of VEGF, FGF-2, IL-8, IL-2, and GM-CSF. These molecules are involved in tumour progression and aggressiveness, and are also involved in a generation of disease associated pain.

scholarly journals Aminopeptidase N/CD13 as a potential therapeutic target in malignant pleural mesothelioma

2018 ◽  
Vol 51 (5) ◽  
pp. 1701610 ◽  
Author(s):  
Takahiko Otsuki ◽  
Taku Nakashima ◽  
Hironobu Hamada ◽  
Yusuke Takayama ◽  
Shin Akita ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Malignant Pleural Mesothelioma ◽  
Poor Prognosis ◽  
Tumour Growth ◽  
Tumour Progression ◽  
Molecular Target ◽  
Aminopeptidase N ◽  
Pleural Mesothelioma ◽  
Tumour Angiogenesis ◽  
Potential Therapeutic Target

Angiogenesis is a crucial factor in the progression of malignant pleural mesothelioma (MPM) and antiangiogenic strategies might be effective against MPM. Aminopeptidase N (APN)/CD13 promotes tumour angiogenesis and is associated with poor prognosis; however, its clinical significance in MPM remains unclear.In 37 consecutive patients with surgically resected MPM, we evaluated the association between immunohistochemical APN/CD13 expression in resected tumours and survival. Additionally, the antitumour and antiangiogenic effects of MT95-4, a fully humanised anti-APN/CD13 monoclonal antibody, were evaluated in mice orthotopically implanted with EHMES-10 (abundantly expressing APN/CD13) and MSTO-211H (scarcely expressing APN/CD13) MPM cells.High tumour APN/CD13 expression was associated with poor prognosis in MPM patients (p=0.04), and MT95-4 treatment reduced tumour growth and angiogenesis in mice harbouring EHMES-10 but not MSTO-211H cells. Furthermore, in mice harbouring EHMES-10 cells, MT95-4 combined with cisplatin more effectively suppressed tumour progression than cisplatin alone.Taken together, these results suggest that APN/CD13 is implicated in the aggressiveness of MPM. Here, MT95-4 treatment reduced tumour progression likely by inhibiting angiogenesis, suggesting APN/CD13 as a potential molecular target for MPM treatment. Additionally, combination treatment with MT95-4 and cisplatin could represent a promising approach to treating MPM exhibiting high APN/CD13 expression.

scholarly journals Recent Insights into Cell Surface Heparan Sulphate Proteoglycans and Cancer

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1541 ◽  
Author(s):  
John R Couchman ◽  
Hinke Multhaupt ◽  
Ralph D. Sanderson
Keyword(s):  
Cell Surface ◽  
Core Protein ◽  
Tumour Progression ◽  
Heparan Sulphate ◽  
Cell Behaviour ◽  
Surface Receptors ◽  
Protein Ligands ◽  
Proliferation And Differentiation ◽  
Cell Processes ◽  
Heparan Sulphate Proteoglycans

A small group of cell surface receptors are proteoglycans, possessing a core protein with one or more covalently attached glycosaminoglycan chains. They are virtually ubiquitous and their chains are major sites at which protein ligands of many types interact. These proteoglycans can signal and regulate important cell processes, such as adhesion, migration, proliferation, and differentiation. Since many protein ligands, such as growth factors, morphogens, and cytokines, are also implicated in tumour progression, it is increasingly apparent that cell surface proteoglycans impact tumour cell behaviour. Here, we review some recent advances, emphasising that many tumour-related functions of proteoglycans are revealed only after their modification in processes subsequent to synthesis and export to the cell surface. These include enzymes that modify heparan sulphate structure, recycling of whole or fragmented proteoglycans into exosomes that can be paracrine effectors or biomarkers, and lateral interactions between some proteoglycans and calcium channels that impact the actin cytoskeleton.

scholarly journals ADAM-Mediated Signalling Pathways in Gastrointestinal Cancer Formation

2020 ◽  
Vol 21 (14) ◽  
pp. 5133
Author(s):  
Neele Schumacher ◽  
Stefan Rose-John ◽  
Dirk Schmidt-Arras
Keyword(s):  
Signal Transduction ◽  
Growth Factors ◽  
Tumour Cell ◽  
Tumour Growth ◽  
Current Knowledge ◽  
Limited Proteolysis ◽  
Signalling Pathways ◽  
Ectodomain Shedding ◽  
The Family ◽  
Gastrointestinal Tumours

Tumour growth is not solely driven by tumour cell-intrinsic mechanisms, but also depends on paracrine signals provided by the tumour micro-environment. These signals comprise cytokines and growth factors that are synthesized as trans-membrane proteins and need to be liberated by limited proteolysis also termed ectodomain shedding. Members of the family of A disintegrin and metalloproteases (ADAM) are major mediators of ectodomain shedding and therefore initiators of paracrine signal transduction. In this review, we summarize the current knowledge on how ADAM proteases on tumour cells but also on cells of the tumour micro-environment contribute to the formation of gastrointestinal tumours, and discuss how these processes can be exploited pharmacologically.

Significance of PI3K signalling pathway in clear cell renal cell carcinoma in relation to VHL and HIF status

2020 ◽  
pp. jclinpath-2020-206693
Author(s):  
Raviprakash Tumkur Sitaram ◽  
Maréne Landström ◽  
Göran Roos ◽  
Börje Ljungberg
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Tumour Progression ◽  
Recent Decade ◽  
Signalling Pathway ◽  
Signalling Pathways ◽  
Cell Renal Cell Carcinoma ◽  
Von Hippel Lindau

Renal cell carcinoma (RCC) includes diverse tumour types characterised by various genetic abnormalities. The genetic changes, like mutations, deletions and epigenetic alterations, play a crucial role in the modification of signalling networks, tumour pathogenesis and prognosis. The most prevalent RCC type, clear cell RCC (ccRCC), is asymptomatic in the early stages and has a poorer prognosis compared with the papillary and the chromophobe types RCCs. Generally, ccRCC is refractory to chemotherapy and radiation therapy. Loss of von Hippel-Lindau (VHL) gene and upregulation of hypoxia-inducible factors (HIF), the signature of most sporadic ccRCC, promote multiple growth factors. Hence, VHL/HIF and a variety of pathways, including phosphatase and TEnsin homolog on chromosome 10/phosphatidylinositol-3-kinase (PI3K)/AKT, are closely connected and contribute to the ontogeny of ccRCC. In the recent decade, multiple targeting agents have been developed based on blocking major signalling pathways directly or indirectly involved in ccRCC tumour progression, metastasis, angiogenesis and survival. However, most of these drugs have limitations; either metastatic ccRCC develops resistance to these agents, or despite blocking receptors, tumour cells use alternate signalling pathways. This review compiles the state of knowledge about the PI3K/AKT signalling pathway confined to ccRCC and its cross-talks with VHL/HIF pathway.

CRYAB inhibits migration and invasion of bladder cancer cells through the PI3K/AKT and ERK pathways

2019 ◽  
Vol 50 (3) ◽  
pp. 254-260 ◽  
Author(s):  
Houxin Ruan ◽  
Yang Li ◽  
Xu Wang ◽  
Bin Sun ◽  
Weihua Fang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Tumour Progression ◽  
Tissue Microarrays ◽  
Mitogen Activated Protein Kinase ◽  
Signalling Pathways ◽  
Migration And Invasion ◽  
High Recurrence Rate ◽  
Mesenchymal Transition ◽  
Alpha Crystallin

Abstract Background Bladder cancer is a common malignancy characterized by a high recurrence rate and the development of drug resistance. Frequent mutations and gene expression alterations in the PI3K/AKT and mitogen-activated protein kinase-ERK pathways lead to deregulated cell growth and the acquisition of invasive properties, which facilitates tumour progression and confers resistance to chemotherapy. Therefore, identification of the underlying mechanisms that trigger the activation of these signalling pathways and control the invasive phenotype of tumour cells is of urgent need. Methods We utilized publicly available gene expression databases (GEO and TCGA) and bioinformatics analysis to identify key gene expression changes in human bladder cancer . The key gene expression was detected using BC tissue microarrays. Cell proliferation, apoptosis, migration, invasion and related signalling pathways were analysed flowing transfection with key gene overexpression plasmids. Results The analysis revealed that inhibited expression of the alpha-crystallin B chain was a common feature in all analysed datasets. The decrease in alpha-crystallin B expression was further confirmed at the protein level using BC tissue microarrays. Overexpression of alpha-crystallin B in T24 and J82 BC cell lines resulted in significant inhibition of tumour cell migration and invasion, which was associated with a decrease in PI3K, AKT and ERK activation. Moreover, alpha-crystallin B overexpression increased the expression of E-cadherin, while reducing the expression of N-cadherin, which indicated suppression of the epithelial–mesenchymal transition. Conclusions Overall, the results of our study suggested that alpha-crystallin B may function as a tumour-suppressive factor in bladder cancer.

scholarly journals Polycystin‐1 affects cancer cell behaviour and interacts with mTOR and Jak signalling pathways in cancer cell lines

2019 ◽  
Vol 23 (9) ◽  
pp. 6215-6227 ◽  
Author(s):  
Kostas A. Papavassiliou ◽  
Ilianna Zoi ◽  
Antonios N. Gargalionis ◽  
Michael Koutsilieris
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Signalling Pathways ◽  
Cell Behaviour

scholarly journals Anti-carcinogenic effects of exercise-conditioned human serum: evidence, relevance and opportunities

2021 ◽  
Author(s):  
Richard S. Metcalfe ◽  
Rachael Kemp ◽  
Shane M. Heffernan ◽  
Rachel Churm ◽  
Yung-Chih Chen ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cancer Cell ◽  
Cancer Biology ◽  
Tumour Growth ◽  
Exercise Physiology ◽  
Future Research ◽  
Cell Behaviour ◽  
Rna Molecules

AbstractRegular physical activity reduces the risk of several site-specific cancers in humans and suppresses tumour growth in animal models. The mechanisms through which exercise reduces tumour growth remain incompletely understood, but an intriguing and accumulating body of evidence suggests that the incubation of cancer cells with post-exercise serum can have powerful effects on key hallmarks of cancer cell behaviour in vitro. This suggests that exercise can impact tumour biology through direct changes in circulating proteins, RNA molecules and metabolites. Here, we provide a comprehensive narrative overview of what is known about the effects of exercise-conditioned sera on in vitro cancer cell behaviour. In doing so, we consider the key limitations of the current body of literature, both from the perspective of exercise physiology and cancer biology, and we discuss the potential in vivo physiological relevance of these findings. We propose key opportunities for future research in an area that has the potential to identify key anti-oncogenic protein targets and optimise physical activity recommendations for cancer prevention, treatment and survivorship.

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