State-of-the-Art: Exosomes in Colorectal Cancer

2021 ◽  
Vol 21 ◽  
Author(s):  
Yan Dang ◽  
Shutian Zhang ◽  
Yongjun Wang ◽  
Guiping Zhao ◽  
Chuyan Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mortality Rate ◽  
Cancer Cells ◽  
Stromal Cells ◽  
State Of The Art ◽  
Therapy Resistance ◽  
Clinical Applications ◽  
Bioactive Molecules ◽  
High Prevalence ◽  
Cancerous Cells

: Colorectal cancer (CRC) has a high prevalence and mortality rate, globally. To date, the progression mechanisms of CRC are still elusive. Exosomes (~100 nm in diameter) correspond to a subset of extracellular vesicles formed by an array of cancerous cells and stromal cells. These particular nanovesicles carry and transmit bioactive molecules, like proteins, lipids, and genetic materials, which mediate the crosstalk between cancer cells and the microenvironment. Accumulating evidence has shown the decisive functions of exosomes in the development, metastasis, and therapy resistance of CRC. Furthermore, some recent studies have also revealed the abilities of exosomes to function as either biomarkers or therapeutic targets for CRC. This review focuses on the specific mechanisms of exosomes in regulating CRC progression, and summarizes the potential clinical applications of exosomes in the diagnosis and therapy of CRC.

scholarly journals Mesenchymal Stromal Cell Secretome for the Treatment of Immune-Mediated Inflammatory Diseases: Latest Trends in Isolation, Content Optimization and Delivery Avenues

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1802
Author(s):  
Elena Munoz-Perez ◽  
Ainhoa Gonzalez-Pujana ◽  
Manoli Igartua ◽  
Edorta Santos-Vizcaino ◽  
Rosa Maria Hernandez
Keyword(s):  
Stromal Cells ◽  
State Of The Art ◽  
Inflammatory Diseases ◽  
Therapeutic Approaches ◽  
Pharmacological Management ◽  
Beneficial Effects ◽  
New Therapeutic Approaches ◽  
Immune Mediated ◽  
High Prevalence ◽  
Inflammatory Processes

Considering the high prevalence and the complex pharmacological management of immune-mediated inflammatory diseases (IMIDs), the search for new therapeutic approaches for their treatment is vital. Although the immunomodulatory and anti-inflammatory effects of mesenchymal stromal cells (MSCs) have been extensively studied as a potential therapy in this field, direct MSC implantation presents some limitations that could slow down the clinical translation. Since the beneficial effects of MSCs have been mainly attributed to their ability to secrete a plethora of bioactive factors, their secretome has been proposed as a new and promising pathway for the treatment of IMIDs. Formed from soluble factors and extracellular vesicles (EVs), the MSC-derived secretome has been proven to elicit immunomodulatory effects that control the inflammatory processes that occur in IMIDs. This article aims to review the available knowledge on the MSC secretome, evaluating the advances in this field in terms of its composition, production and application, as well as analyzing the pending challenges in the field. Moreover, the latest research involving secretome administration in IMIDs is discussed to provide an updated state-of-the-art for this field. Finally, novel secretome delivery alternatives are reviewed, paying special attention to hydrogel encapsulation as one of the most convenient and promising strategies.

scholarly journals Metabolic cooperation between cancer and non-cancerous stromal cells is pivotal in cancer progression

Tumor Biology ◽  
2018 ◽  
Vol 40 (2) ◽  
pp. 101042831875620 ◽  
Author(s):  
Filipa Lopes-Coelho ◽  
Sofia Gouveia-Fernandes ◽  
Jacinta Serpa
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Inflammatory Cells ◽  
Metabolic Adaptation ◽  
Metabolic Cooperation ◽  
Metabolic Remodeling ◽  
Organ Tissue ◽  
Cancerous Cells

The way cancer cells adapt to microenvironment is crucial for the success of carcinogenesis, and metabolic fitness is essential for a cancer cell to survive and proliferate in a certain organ/tissue. The metabolic remodeling in a tumor niche is endured not only by cancer cells but also by non-cancerous cells that share the same microenvironment. For this reason, tumor cells and stromal cells constitute a complex network of signal and organic compound transfer that supports cellular viability and proliferation. The intensive dual-address cooperation of all components of a tumor sustains disease progression and metastasis. Herein, we will detail the role of cancer-associated fibroblasts, cancer-associated adipocytes, and inflammatory cells, mainly monocytes/macrophages (tumor-associated macrophages), in the remodeling and metabolic adaptation of tumors.

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 Interleukin Receptor Antagonist Inhibits Matastatic Potential by Down-Regulating CXCL12/CXCR4 Signaling Axis in Colorectal Cancer

2021 ◽  
Author(s):  
Jiachi Ma ◽  
Wanqing Liang ◽  
Yaosheng Qiang ◽  
Lei Li ◽  
Jun Du ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Stromal Cells ◽  
Metastatic Potential ◽  
Colorectal Cancer Cell ◽  
Colorectal Cancer Cells ◽  
Ht 29 ◽  
High Liver

Abstract Background: The aim of this study was to investigate the co-operative role of CXCR4/ CXCL12 axis and IL-1Ra in metastatic processes mechanism by interactions between colorectal cancer cells and stromal cells in their microenvironment. Methods: Expression of IL-1a, CXCL12 and CXCR4 mRNA and proteins were determined by RT-PCR and Western blot. The effect of secreted level of CXCL12 by IL-1Ra on fibroblasts was measured by ELISA. CXCL12 regulate metastatic potential of colorectal cancer was evaluated by proliferation, invasion and angiogenesis assays, respectively, in which invasion and angiogenesis assays used an in vitro system consisting of co-cultured colorectal cells and stromal cells. Results: IL-1a was expressed in high liver metastatic colorectal cancer cell lines (HT-29 and WiDr). The colorectal cancer cell-derived IL-1a and rIL-1a significantly promoted CXCL12 expression by fibroblasts, and this enhancing effect can be significantly inhibited by IL-1Ra (P<0.01). CXCL12 not only enhanced the migration and proliferation of human umbilical vein endothelial cells (HUVECs), but also significantly enhanced angiogenesis (P<0.01). Furthermore, the high liver-metastatic colorectal cancer cell line (HT-29), which secretes IL-1a, significantly enhanced angiogenesis compared to the low liver-metastatic cell line (CaCo-2), which does not produce IL-1a (P<0.01). On the contrary, IL-1Ra can significantly inhibit migration, proliferation and angiogenesis (P<0.01). Conclusion: Autocrine IL-1a and paracrine CXCL12 co-enhances the metastatic potential of colorectal cancer cells; IL-1Ra can inhibit the metastatic potential of colorectal cancer cells via decrease IL-1a/CXCR4/CXCL12 signaling pathways.

scholarly journals Exosomal MicroRNAs Mediating Crosstalk Between Cancer Cells With Cancer-Associated Fibroblasts and Tumor-Associated Macrophages in the Tumor Microenvironment

2021 ◽  
Vol 11 ◽  
Author(s):  
Tong Su ◽  
Panpan Zhang ◽  
Fujun Zhao ◽  
Shu Zhang
Keyword(s):  
Tumor Progression ◽  
Cancer Cells ◽  
Stromal Cells ◽  
Current Knowledge ◽  
Bioactive Molecules ◽  
Cancer Associated Fibroblasts ◽  
Tumor Associated Macrophages ◽  
Non Coding Rna ◽  
Different Types ◽  
Exosomal Mirna

Exosomes are small extracellular vesicles containing diverse bioactive molecules. They play essential roles in mediating bidirectional interplay between cancer and stromal cells. Specific elements are selected into different types of exosomes via various mechanisms, including microRNAs (miRNAs), a subset of non-coding RNA that could epigenetically reprogram cells and modulate their activities. Cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) are two major types of stromal cells inhibiting immune response and facilitating tumor progression. Notably, accumulated studies provided critical evidence regarding the significance of exosomal miRNA–mediated intercellular crosstalk between cancer cells with TAMs and CAFs for tumor progression. This review aimed to summarize the current knowledge of cell–cell interactions between stromal and cancer cells conveyed by exosome-derived miRNAs. The findings might help find effective therapeutic targets of cancer.

scholarly journals Immune Escape Mechanisms in Colorectal Cancer Pathogenesis and Liver Metastasis

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Massimo Pancione ◽  
Guido Giordano ◽  
Andrea Remo ◽  
Antonio Febbraro ◽  
Lina Sabatino ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Immune Escape ◽  
De Novo ◽  
Tumour Progression ◽  
Therapy Resistance ◽  
Phenotypic Traits ◽  
Metastatic Progression ◽  
Malignant Cells ◽  
Cancer Pathogenesis

Over the past decade, growing evidence indicates that the tumor microenvironment (TME) contributes with genomic/epigenomic aberrations of malignant cells to enhance cancer cells survival, invasion, and dissemination. Many factors, produced orde novosynthesized by immune, stromal, or malignant cells, acting in a paracrine and autocrine fashion, remodel TME and the adaptive immune response culminating in metastasis. Taking into account the recent accomplishments in the field of immune oncology and using metastatic colorectal cancer (mCRC) as a model, we propose that the evasion of the immune surveillance and metastatic spread can be achieved through a number of mechanisms that include (a) intrinsic plasticity and adaptability of immune and malignant cells to paracrine and autocrine stimuli or genotoxic stresses; (b) alteration of positional schemes of myeloid-lineage cells, produced by factors controlling the balance between tumour-suppressing and tumour-promoting activities; (c) acquisition by cancer cells of aberrant immune-phenotypic traits (NT5E/CD73, CD68, and CD163) that enhance the interactions among TME components through the production of immune-suppressive mediators. These properties may represent the driving force of metastatic progression and thus clinically exploitable for cancer prevention and therapy. In this review we summarize results and suggest new hypotheses that favour the growing impact of tumor-infiltrating immune cells on tumour progression, metastasis, and therapy resistance.

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.

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