scholarly journals Exosomes in Cancer: Circulating Immune-Related Biomarkers

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Alicja Głuszko ◽  
Mirosław J. Szczepański ◽  
Nils Ludwig ◽  
Shafaq M. Mirza ◽  
Wioletta Olejarz
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Stromal Cells ◽  
Therapy Resistance ◽  
Tumor Biomarker ◽  
Systemic Effects ◽  
Multivesicular Bodies ◽  
Metastatic Niche ◽  
Patients With Cancer ◽  
Niche Formation

Exosomes, the smallest vesicles (30–100 nm) among multivesicular bodies, are released by all body cells including tumor cells. The cargo they transfer plays an important role in intercellular communication. Tumor-derived exosomes (TEXs) maintain interactions between cancer cells and the microenvironment. Emerging evidence suggests that tumor cells release a large number of exosomes, which may not only influence proximal tumor cells and stromal cells in the local microenvironment but can also exert systemic effects as they are circulating in the blood. TEXs have been shown to boost tumor growth promote progression and metastatic spread via suppression or modification of the immune response towards cancer cells, regulation of tumor neo-angiogenesis, pre-metastatic niche formation, and therapy resistance. In addition, recent studies in patients with cancer suggest that TEXs could serve as tumor biomarker reflecting partially the genetic and molecular content of the parent cancer cell (i.e., as a so-called “liquid biopsy”). Furthermore, recent studies have demonstrated that exosomes may have immunotherapeutic applications, or can act as a drug delivery system for targeted therapies with drugs and biomolecules.

scholarly journals The dynamic behavior of lipid droplets in the pre-metastatic niche

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Chunliang Shang ◽  
Jie Qiao ◽  
Hongyan Guo
Keyword(s):  
Tumor Cells ◽  
Immune Cells ◽  
Stromal Cells ◽  
Lipid Droplets ◽  
Metastatic Tumor ◽  
Current Evidence ◽  
Biological Functions ◽  
Metastatic Niche ◽  
Niche Formation

AbstractThe pre-metastatic niche is a favorable microenvironment for the colonization of metastatic tumor cells in specific distant organs. Lipid droplets (LDs, also known as lipid bodies or adiposomes) have increasingly been recognized as lipid-rich, functionally dynamic organelles within tumor cells, immune cells, and other stromal cells that are linked to diverse biological functions and human diseases. Moreover, in recent years, several studies have described the indispensable role of LDs in the development of pre-metastatic niches. This review discusses current evidence related to the biogenesis, composition, and functions of LDs related to the following characteristics of the pre-metastatic niche: immunosuppression, inflammation, angiogenesis/vascular permeability, lymphangiogenesis, organotropism, reprogramming. We also address the function of LDs in mediating pre-metastatic niche formation. The potential of LDs as markers and targets for novel antimetastatic therapies will be discussed.

scholarly journals The Role of Cancer-Associated Fibroblasts and Extracellular Vesicles in Tumorigenesis

2020 ◽  
Vol 21 (18) ◽  
pp. 6837 ◽  
Author(s):  
Issraa Shoucair ◽  
Fernanda Weber Mello ◽  
James Jabalee ◽  
Saeideh Maleki ◽  
Cathie Garnis
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Therapy Resistance ◽  
The Other ◽  
Cancer Associated Fibroblasts ◽  
Metastatic Niche ◽  
Niche Formation ◽  
Molecular Aspects

Extracellular vesicles (EVs) play a key role in the communication between cancer cells and stromal components of the tumor microenvironment (TME). In this context, cancer cell-derived EVs can regulate the activation of a CAF phenotype in TME cells, which can be mediated by several EV cargos (e.g., miRNA, proteins, mRNA and lncRNAs). On the other hand, CAF-derived EVs can mediate several processes during tumorigenesis, including tumor growth, invasion, metastasis, and therapy resistance. This review aimed to discuss the molecular aspects of EV-based cross-talk between CAFs and cancer cells during tumorigenesis, in addition to assessing the roles of EV cargo in therapy resistance and pre-metastatic niche formation.

scholarly journals Tumor secreted ANGPTL2 facilitates recruitment of neutrophils to the lung to promote lung pre-metastatic niche formation and targeting ANGPTL2 receptor signaling prevents metastatic disease.

2019 ◽  
Author(s):  
Manish Charan ◽  
Piyush Dravid ◽  
Maren Cam ◽  
Bhuvana Setty ◽  
Ryan D Roberts ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Primary Tumor ◽  
Neutrophil Recruitment ◽  
Lung Epithelial Cells ◽  
Metastatic Niche ◽  
Lung Epithelial ◽  
Niche Formation

Abstract Abstract Background: The pre-metastatic niche (PMN) represents an abnormal microenvironment devoid of cancer cells, but favoring tumor growth. Little is known about the mechanisms that generate the PMN or their effects on host cells within metastasis-prone organs. Osteosarcoma is a malignant tumor of bone made devastating through aggressive metastatic spread primarily to the lung. Mechanisms driving this tropism for lung tissue remain elusive though likely invoke specific interactions between tumor cells and the lung microenvironment. Methods: By using spontaneous metastatic models, we investigated whether lung epithelial cells are essential for primary tumor induced neutrophil recruitment in lung and subsequently initiating PMN formation in osteosarcoma. Effects of a non–RGD-based integrin binding peptide (ATN-161) on osteosarcoma metastasis was examined in tail-vein mouse injection model. Results: Serum levels of ANGPTL2 in osteosarcoma patients are significantly higher compared to those in healthy controls. Tumor-derived ANGPTL2 stimulates lung epithelial cells, which is essential for primary tumor-induced neutrophil recruitment in lung and subsequent pre-metastatic niche formation. In addition, tumor cell-derived ANGPTL2 disrupts vascular endothelial cell-cell junctions, increases the permeability of lung capillaries, and facilitates the trans-endothelial passage of tumor cells. Furthermore, we showed that pharmaceutical inhibition of ANGPTL2 signaling by ATN-161 diminished metastatic load in lungs likely due to reduction of the lung pre-metastatic niche formation. Conclusions: Our data provide plausible evidence that activation of lung epithelial α5β1 receptor by ANGPTL2 induces chemokine production and neutrophil recruitment causing tumor growth-favoring lung microenvironment for incoming metastatic cancer cells. Pharmaceutical inhibition of ANGPTL2 signaling by ATN-161 diminished metastatic load suggesting possible therapeutic utility of ATN-161 in early stage osteosarcoma in children.

scholarly journals Production of Adenosine by Ectonucleotidases: A Key Factor in Tumor Immunoescape

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
François Ghiringhelli ◽  
Mélanie Bruchard ◽  
Fanny Chalmin ◽  
Cédric Rébé
Keyword(s):  
Immune Response ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Stromal Cells ◽  
T Cell Response ◽  
Antitumor Immune Response ◽  
Tumor Bed ◽  
Wide Range ◽  
Key Factor ◽  
The Impact

It is now well known that tumor immunosurveillance contributes to the control of cancer growth. Many mechanisms can be used by cancer cells to avoid the antitumor immune response. One such mechanism relies on the capacity of cancer cells or more generally of the tumor microenvironment to generate adenosine, a major molecule involved in antitumor T cell response suppression. Adenosine is generated by the dephosphorylation of extracellular ATP released by dying tumor cells. The conversion of ATP into adenosine is mediated by ectonucleotidase molecules, namely, CD73 and CD39. These molecules are frequently expressed in the tumor bed by a wide range of cells including tumor cells, regulatory T cells, Th17 cells, myeloid cells, and stromal cells. Recent evidence suggests that targeting adenosine by inhibiting ectonucleotidases may restore the resident antitumor immune response or enhance the efficacy of antitumor therapies. This paper will underline the impact of adenosine and ectonucleotidases on the antitumor response.

scholarly journals Control of metastatic niche formation by targeting APBA3/Mint3 in inflammatory monocytes

2017 ◽  
Vol 114 (22) ◽  
pp. E4416-E4424 ◽  
Author(s):  
Toshiro Hara ◽  
Hiroki J. Nakaoka ◽  
Tetsuro Hayashi ◽  
Kouhei Mimura ◽  
Daisuke Hoshino ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Neutralizing Antibody ◽  
Complete Suppression ◽  
Metastatic Niche ◽  
Macrophage Function ◽  
Inflammatory Monocytes ◽  
Niche Formation ◽  
Metastatic Sites

Cancer metastasis is intricately orchestrated by both cancer and normal cells, such as endothelial cells and macrophages. Monocytes/macrophages, which are often co-opted by cancer cells and promote tumor malignancy, acquire more than half of their energy from glycolysis even during normoxic conditions. This glycolytic activity is maintained during normoxia by the functions of hypoxia inducible factor 1 (HIF-1) and its activator APBA3. The mechanism by which APBA3 inhibition partially suppresses macrophage function and affects cancer metastasis is of interest in view of avoidance of the adverse effects of complete suppression of macrophage function during therapy. Here, we report that APBA3-deficient mice show reduced metastasis, with no apparent effect on primary tumor growth. APBA3 deficiency in inflammatory monocytes, which strongly express the chemokine receptor CCR2 and are recruited toward chemokine CCL2 from metastatic sites, hampers glycolysis-dependent chemotaxis of cells toward metastatic sites and inhibits VEGFA expression, similar to the effects observed with HIF-1 deficiency. Host APBA3 induces VEGFA-mediated E-selectin expression in the endothelial cells of target organs, thereby promoting extravasation of cancer cells and micrometastasis formation. Administration of E-selectin–neutralizing antibody also abolished host APBA3-mediated metastatic formation. Thus, targeting APBA3 is useful for controlling metastatic niche formation by inflammatory monocytes.

scholarly journals Exosome-Derived ADAM17 Promotes Liver Metastasis in Colorectal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Jinbing Sun ◽  
Zhihua Lu ◽  
Wei Fu ◽  
Kuangyi Lu ◽  
Xiuwen Gu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Metastatic Niche ◽  
Colorectal Cancer Cells ◽  
Niche Formation ◽  
Underlying Mechanisms

Exosomes derived from cancer cells are deemed important drivers of pre-metastatic niche formation at distant organs, but the underlying mechanisms of their effects remain largely unknow. Although the role of ADAM17 in cancer cells has been well studied, the secreted ADAM17 effects transported via exosomes are less understood. Herein, we show that the level of exosome-derived ADAM17 is elevated in the serum of patients with metastatic colorectal cancer as well as in metastatic colorectal cancer cells. Furthermore, exosomal ADAM17 was shown to promote the migratory ability of colorectal cancer cells by cleaving the E-cadherin junction. Moreover, exosomal ADAM17 overexpression as well as RNA interference results highlighted its function as a tumor metastasis-promoting factor in colorectal cancer in vitro and in vivo. Taken together, our current work suggests that exosomal ADAM17 is involved in pre-metastatic niche formation and may be utilized as a blood-based biomarker of colorectal cancer metastasis.

scholarly journals Cancer-associated Fibroblasts: Origins, Heterogeneity and Functions in Tumor Microenvironment

2020 ◽  
Author(s):  
Kevin Dzobo
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Tumor Stroma ◽  
Bioinformatic Analysis ◽  
Therapy Resistance ◽  
Response To Therapy ◽  
The Cancer Genome Atlas ◽  
Cancer Associated Fibroblasts

Current therapeutic strategies targeting cancer cells within solid tumors have displayed limited success owing to the presence of non-cancer components referred to as the tumor stroma within the tumor microenvironment (TM). These stromal cells, extracellular matrix and blood vessels influence cancer cell response to therapy and play key roles in tumor relapse and resistance. Of the stromal cells present in the TM, a lot of attention has been given to cancer-associated fibroblasts (CAFs) as they are the most abundant and are important in cancer initiation, progression and therapy resistance. In this updated review I emphasize the role of CAFs in the regulation of tumor cell behaviour and reveal how CAF-derived factors and signaling influence tumor cell heterogeneity and development of novel strategies to combat cancer. To investigate the expression of CAF markers in tumor tissues versus normal tissues, transcriptomic data from The Cancer Genome Atlas (TCGA) and the Gene Expression Profiling Interactive Analysis (GEPIA) databases was used. Bioinformatic analysis reveals differential expression of CAF markers in several cancer types, underscoring the need for further multiomics and biochemical studies on CAFs, CAF subsets and markers. Differences in CAF markers’ expression could be due to different cellular origins as well as the effect of cancer-specific tumor microenvironmental effect on CAFs. Lastly, I present recent advances in therapeutic targeting of CAFs and the success of such endeavours or its lack thereof. It is recommended that for patients’ outcomes to improve, cancer treatment be combinatorial in nature, targeting both cancer cells and stromal cells and interactions.

scholarly journals Emerging Role of Extracellular Vesicles and Cellular Communication in Metastasis

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3429
Author(s):  
Aisling Forder ◽  
Chi-Yun Hsing ◽  
Jessica Trejo Vazquez ◽  
Cathie Garnis
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Treatment Strategies ◽  
Metastatic Niche ◽  
Novel Treatment ◽  
Membrane Bound ◽  
Novel Treatment Strategies

Communication between cancer cells and the surrounding stromal cells of the tumor microenvironment (TME) plays a key role in promoting metastasis, which is the major cause of cancer death. Small membrane-bound particles called extracellular vesicles (EVs) are released from both cancer and stromal cells and have a key role in mediating this communication through transport of cargo such as various RNA species (mRNA, miRNA, lncRNA), proteins, and lipids. Tumor-secreted EVs have been observed to induce a pro-tumorigenic phenotype in non-malignant cells of the stroma, including fibroblasts, endothelial cells, and local immune cells. These cancer-associated cells then drive metastasis by mechanisms such as increasing the invasiveness of cancer cells, facilitating angiogenesis, and promoting the formation of the pre-metastatic niche. This review will cover the role of EV-mediated signaling in the TME during metastasis and highlight the therapeutic potential of targeting these pathways to develop biomarkers and novel treatment strategies.

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