scholarly journals Dissecting the role of tissue-specific cancer-associated fibroblasts in the prostate tumour microenvironment

2021 ◽  
Author(s):  
Anna Jaeschke
Keyword(s):  
Tumour Microenvironment ◽  
Cancer Associated Fibroblasts ◽  
Tissue Specific ◽  
Prostate Tumour ◽  
Specific Cancer

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.

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.

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 Influence the Biological Properties of Malignant Tumours via Paracrine Secretion and Exosome Production

2022 ◽  
Vol 23 (2) ◽  
pp. 964
Author(s):  
Martin Vokurka ◽  
Lukáš Lacina ◽  
Jan Brábek ◽  
Michal Kolář ◽  
Yi Zhen Ng ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Tumour Microenvironment ◽  
Biological Properties ◽  
Cancer Associated Fibroblasts ◽  
Malignant Tumours ◽  
Mediated Communication ◽  
Cancer Cell Population ◽  
Differentiation Status

Cancer-associated fibroblasts (CAFs) are an essential component of the tumour microenvironment. They represent a heterogeneous group of cells that are under the control of cancer cells and can reversely influence the cancer cell population. They affect the cancer cell differentiation status, and the migration and formation of metastases. This is achieved through the production of the extracellular matrix and numerous bioactive factors. IL-6 seems to play the central role in the communication of noncancerous and cancer cells in the tumour. This review outlines the role of exosomes in cancer cells and cancer-associated fibroblasts. Available data on the exosomal cargo, which can significantly intensify interactions in the tumour, are summarised. The role of exosomes as mediators of the dialogue between cancer cells and cancer-associated fibroblasts is discussed together with their therapeutic relevance. The functional unity of the paracrine- and exosome-mediated communication of cancer cells with the tumour microenvironment represented by CAFs is worthy of attention.

scholarly journals Activation of the GPR35 pathway drives angiogenesis in the tumour microenvironment

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323363
Author(s):  
Ester Pagano ◽  
Joshua E Elias ◽  
Georg Schneditz ◽  
Svetlana Saveljeva ◽  
Lorraine M Holland ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumour Growth ◽  
Tumour Microenvironment ◽  
Tube Formation ◽  
Tissue Remodelling ◽  
Colon Cancers ◽  
Inflammatory Bowel ◽  
Ion Pumping ◽  
G Protein Coupled

ObjectivePrimary sclerosing cholangitis (PSC) is in 70% of cases associated with inflammatory bowel disease. The hypermorphic T108M variant of the orphan G protein-coupled receptor GPR35 increases risk for PSC and ulcerative colitis (UC), conditions strongly predisposing for inflammation-associated liver and colon cancer. Lack of GPR35 reduces tumour numbers in mouse models of spontaneous and colitis associated cancer. The tumour microenvironment substantially determines tumour growth, and tumour-associated macrophages are crucial for neovascularisation. We aim to understand the role of the GPR35 pathway in the tumour microenvironment of spontaneous and colitis-associated colon cancers.DesignMice lacking GPR35 on their macrophages underwent models of spontaneous colon cancer or colitis-associated cancer. The role of tumour-associated macrophages was then assessed in biochemical and functional assays.ResultsHere, we show that GPR35 on macrophages is a potent amplifier of tumour growth by stimulating neoangiogenesis and tumour tissue remodelling. Deletion of Gpr35 in macrophages profoundly reduces tumour growth in inflammation-associated and spontaneous tumour models caused by mutant tumour suppressor adenomatous polyposis coli. Neoangiogenesis and matrix metalloproteinase activity is promoted by GPR35 via Na/K-ATPase-dependent ion pumping and Src activation, and is selectively inhibited by a GPR35-specific pepducin. Supernatants from human inducible-pluripotent-stem-cell derived macrophages carrying the UC and PSC risk variant stimulate tube formation by enhancing the release of angiogenic factors.ConclusionsActivation of the GPR35 pathway promotes tumour growth via two separate routes, by directly augmenting proliferation in epithelial cells that express the receptor, and by coordinating macrophages’ ability to create a tumour-permissive environment.

scholarly journals Cancer, Retrogenes, and Evolution

Life ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 72
Author(s):  
Klaudia Staszak ◽  
Izabela Makałowska
Keyword(s):  
Specific Resistance ◽  
Neoplastic Transformation ◽  
Resistance Mechanisms ◽  
Response To Therapy ◽  
Additional Gene ◽  
Cancer Subtypes ◽  
Gene Copies ◽  
Specific Cancer ◽  
Evolution Of Genomes

This review summarizes the knowledge about retrogenes in the context of cancer and evolution. The retroposition, in which the processed mRNA from parental genes undergoes reverse transcription and the resulting cDNA is integrated back into the genome, results in additional copies of existing genes. Despite the initial misconception, retroposition-derived copies can become functional, and due to their role in the molecular evolution of genomes, they have been named the “seeds of evolution”. It is convincing that retrogenes, as important elements involved in the evolution of species, also take part in the evolution of neoplastic tumors at the cell and species levels. The occurrence of specific “resistance mechanisms” to neoplastic transformation in some species has been noted. This phenomenon has been related to additional gene copies, including retrogenes. In addition, the role of retrogenes in the evolution of tumors has been described. Retrogene expression correlates with the occurrence of specific cancer subtypes, their stages, and their response to therapy. Phylogenetic insights into retrogenes show that most cancer-related retrocopies arose in the lineage of primates, and the number of identified cancer-related retrogenes demonstrates that these duplicates are quite important players in human carcinogenesis.

scholarly journals Cancer-Associated Fibroblasts as Players in Cancer Development and Progression and Their Role in Targeted Radionuclide Imaging and Therapy

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1100
Author(s):  
Sofia Koustoulidou ◽  
Mark W. H. Hoorens ◽  
Simone U. Dalm ◽  
Shweta Mahajan ◽  
Reno Debets ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Tumour Microenvironment ◽  
Therapeutic Interventions ◽  
Great Promise ◽  
Cancer Associated Fibroblasts ◽  
Functional Heterogeneity ◽  
Radioligand Therapy ◽  
Targeted Interventions ◽  
Theranostic Applications ◽  
Complex Origin

Cancer Associated Fibroblasts (CAFs) form a major component of the tumour microenvironment, they have a complex origin and execute diverse functions in tumour development and progression. As such, CAFs constitute an attractive target for novel therapeutic interventions that will aid both diagnosis and treatment of various cancers. There are, however, a few limitations in reaching successful translation of CAF targeted interventions from bench to bedside. Several approaches targeting CAFs have been investigated so far and a few CAF-targeting tracers have successfully been developed and applied. This includes tracers targeting Fibroblast Activation Protein (FAP) on CAFs. A number of FAP-targeting tracers have shown great promise in the clinic. In this review, we summarize our current knowledge of the functional heterogeneity and biology of CAFs in cancer. Moreover, we highlight the latest developments towards theranostic applications that will help tumour characterization, radioligand therapy and staging in cancers with a distinct CAF population.

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