bims-exocan 2023-08-06 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2023–08–06
six papers selected by
Muhammad Rizwan, COMSATS University

Recent advances of exosomal circRNAs in cancer and their potential clinical applications.
Exosomal PGAM1 promotes prostate cancer angiogenesis and metastasis by interacting with ACTG1.
Tumor cells-derived exosomal PD-L1 promotes the growth and invasion of lung cancer cells <em>in vitro via</em> mediating macrophages M2 polarization.
Exosomal hsa_circ_000200 as a potential biomarker and metastasis enhancer of gastric cancer via miR-4659a/b-3p/HBEGF axis.
Role of exosomes in transferring chemoresistance through modulation of cancer glycolytic cell metabolism.
Exosomes: Another intercellular lipometabolic communication mediators in digestive system neoplasms?

J Transl Med. 2023 07 31. 21(1): 516

Recent advances of exosomal circRNAs in cancer and their potential clinical applications.

Qian Yi, Jiaji Yue, Yang Liu, Houyin Shi, Wei Sun, Jianguo Feng, Weichao Sun.

  Circular RNA (circRNA) is a type of non-coding RNA that forms a covalently closed, uninterrupted loop. The expression of circRNA differs among cell types and tissues, and various circRNAs are aberrantly expressed in a variety of diseases, including cancer. Aberrantly expressed circRNAs contribute to disease progression by acting as microRNA sponges, functional protein sponges, or novel templates for protein translation. Recent studies have shown that circRNAs are enriched in exosomes. Exosomes are spherical bilayer vesicles released by cells into extracellular spaces that mediate intercellular communication by delivering cargoes. These cargoes include metabolites, proteins, lipids, and RNA molecules. Exosome-mediated cell-cell or cell-microenvironment communications influence the progression of carcinogenesis by regulating cell proliferation, angiogenesis, metastasis as well as immune escape. In this review, we summarize the current knowledge about exosomal circRNAs in cancers and discuss their specific functions in tumorigenesis. Additionally, we discuss the potential value of exosomal circRNAs as diagnostic biomarkers and the potential applications of exosomal circRNA-based cancer therapy.

Keywords:  Cancer treatment; Disgnostic biomarker; Exosome; Tumorigenesis; circRNAs

DOI:  https://doi.org/10.1186/s12967-023-04348-4
Cell Death Dis. 2023 Aug 04. 14(8): 502

Exosomal PGAM1 promotes prostate cancer angiogenesis and metastasis by interacting with ACTG1.

Jun-Qi Luo, Tao-Wei Yang, Jun Wu, Hou-Hua Lai, Li-Bin Zou, Wen-Bin Chen, Xu-Min Zhou, Dao-Jun Lv, Sheng-Ren Cen, Zi-Ning Long, Yi-You Mao, Peng-Xiang Zheng, Xiao-Hong Su, Zhi-Yong Xian, Fang-Peng Shu, Xiang-Ming Mao.

Tumor-derived exosomes and their contents promote cancer metastasis. Phosphoglycerate mutase 1 (PGAM1) is involved in various cancer-related processes. Nevertheless, the underlying mechanism of exosomal PGAM1 in prostate cancer (PCa) metastasis remains unclear. In this study, we performed in vitro and in vivo to determine the functions of exosomal PGAM1 in the angiogenesis of patients with metastatic PCa. We performed Glutathione-S-transferase pulldown, co-immunoprecipitation, western blotting and gelatin degradation assays to determine the pathway mediating the effect of exosomal PGAM1 in PCa. Our results revealed a significant increase in exosomal PGAM1 levels in the plasma of patients with metastatic PCa compared to patients with non-metastatic PCa. Furthermore, PGAM1 was a key factor initiating PCa cell metastasis by promoting invadopodia formation and could be conveyed by exosomes from PCa cells to human umbilical vein endothelial cells (HUVECs). In addition, exosomal PGAM1 could bind to γ-actin (ACTG1), which promotes podosome formation and neovascular sprouting in HUVECs. In vivo results revealed exosomal PGAM1 enhanced lung metastasis in nude mice injected with PCa cells via the tail vein. In summary, exosomal PGAM1 promotes angiogenesis and could be used as a liquid biopsy marker for PCa metastasis.

DOI: https://doi.org/10.1038/s41419-023-06007-4
Eur J Histochem. 2023 Aug 01. 67(3):

Tumor cells-derived exosomal PD-L1 promotes the growth and invasion of lung cancer cells <em>in vitro via</em> mediating macrophages M2 polarization.

Xiangjun Lu, Jian Shen, Siyuan Huang, Dongdong Liu, Haitao Wang.

Lung cancer originating from the bronchial epithelium is the most common lung malignancy. It has been reported that programmed cell death 1 ligand 1 (PD-L1) and tumor-associated macrophages are closely related to the development of lung cancer. However, whether tumor-derived exosomal PD-L1 could mediate the regulation of macrophage polarization in lung cancer remains unclear. For this research, the level of PD-L1 in normal tissues and lung cancer tissues was evaluated using RT-qPCR. Next, the apoptosis of lung cancer cells was evaluated using flow cytometry assay. Then, the structure and morphology of vesicles were observed using transmission electron microscopy and nanoparticle tracking analysis. Later on, the internalization of exosomes by macrophage was observed using fluorescence microscopy. Our results showed that the level of PD-L1 was upregulated in tumor tissues and lung cancer cells. Knockdown of PD-L1 notably inhibited the viability, migration and invasion of lung cancer cells. In addition, lung cancer cells-derived exosomal PD-L1 could be absorbed by macrophages. Meanwhile, exosomal PD-L1 was able to promote macrophages M2 polarization. Moreover, macrophages M2 polarization induced by exosomal PD-L1 further remarkably promoted the viability, migration, invasion, and epithelial-mesenchymal transition process of lung cancer cells. Collectively, knockdown of PD-L1 notably inhibited the viability, migration and invasion of lung cancer cells. Tumor cell-derived exosomal PD-L1 could promote the growth of lung cancer cells by mediating macrophages M2 polarization. Thus, inhibiting macrophages M2 polarization might be a promoting therapy for the treatment of lung cancer.

DOI: https://doi.org/10.4081/ejh.2023.3784
Cancer Cell Int. 2023 Aug 01. 23(1): 151

Exosomal hsa_circ_000200 as a potential biomarker and metastasis enhancer of gastric cancer via miR-4659a/b-3p/HBEGF axis.

Xiao-Juan Huang, Yan Wang, Hui-Ting Wang, Zhao-Feng Liang, Cheng Ji, Xiao-Xi Li, Lei-Lei Zhang, Run-Bi Ji, Wen-Rong Xu, Jian-Hua Jin, Hui Qian.

   BACKGROUND: Exosome, a component of liquid biopsy, loaded protein, DNA, RNA and lipid gradually emerges as biomarker in tumors. However, exosomal circRNAs as biomarker and function mechanism in gastric cancer (GC) are not well understood.
METHODS: Differentially expressed circRNAs in GC and healthy people were screened by database. The identification of hsa_circ_000200 was verified by RNase R and sequencing, and the expression of hsa_circ_000200 was evaluated using qRT-PCR. The biological function of hsa_circ_000200 in GC was verified in vitro. Western blot, RIP, RNA fluorescence in situ hybridization, and double luciferase assay were utilized to explore the potential mechanism of hsa_circ_000200.
RESULTS: Hsa_circ_000200 up-regulated in GC tissue, serum and serum exosomes. Hsa_circ_000200 in serum exosomes showed better diagnostic ability than that of tissues and serum. Combined with clinicopathological parameters, its level was related to invasion depth, TNM staging, and distal metastasis. Functionally, knockdown of hsa_circ_000200 inhibited GC cells proliferation, migration and invasion in vitro, while its overexpression played the opposite role. Importantly, exosomes with up-regulated hsa_circ_000200 promoted the proliferation and migration of co-cultured GC cells. Mechanistically, hsa_circ_000200 acted as a "ceRNA" for miR-4659a/b-3p to increase HBEGF and TGF-β/Smad expression, then promoted the development of GC.
CONCLUSIONS: Our findings suggest that hsa_circ_000200 promotes the progression of GC through hsa_circ_000200/miR-4659a/b-3p/HBEGF axis and affecting the expression of TGF-β/Smad. Serum exosomal hsa_circ_000200 may serve as a potential biomarker for GC.

Keywords:  Exosomes; Gastric cancer; HBEGF; Liquid biopsy marker; hsa_circ_000200; miR-4659a/b-3p

DOI:  https://doi.org/10.1186/s12935-023-02976-w
Cytokine Growth Factor Rev. 2023 Jul 29. pii: S1359-6101(23)00035-7. [Epub ahead of print]

Role of exosomes in transferring chemoresistance through modulation of cancer glycolytic cell metabolism.

Mahrou Vahabi, Annalisa Comandatore, Marika A Franczak, Ryszard T Smolenski, Godefridus J Peters, Luca Morelli, Elisa Giovannetti.

  Chemoresistance constitute a major obstacle in cancer treatment, leading to limited options and decreased patient survival. Recent studies have revealed a novel mechanism of chemoresistance acquisition: the transfer of information via exosomes, small vesicles secreted by various cells. Exosomes play a crucial role in intercellular communication by carrying proteins, nucleic acids, and metabolites, influencing cancer cell behavior and response to treatment. One crucial mechanism of resistance is cancer metabolic reprogramming, which involves alterations in the cellular metabolic pathways to support the survival and proliferation of drug-resistant cancer cells. This metabolic reprogramming often includes increased glycolysis, providing cancer cells with the necessary energy and building blocks to evade the effects of chemotherapy. Notably, exosomes have been found to transport glycolytic enzymes, as identified in proteomic profiling, leading to the reprogramming of metabolic pathways, facilitating altered glucose metabolism and increased lactate production. As a result, they profoundly impact the tumor microenvironment, promoting tumor progression, survival, immune evasion, and drug resistance.Understanding the complexities of such exosome-mediated cell-to-cell communication might open new therapeutic avenues and facilitate biomarker development in managing cancers characterized by aggressive glycolytic features. Moreover, given the intricate nature of metabolic abnormalities combining future exosome-based-targeted therapies with existing treatments like chemotherapy, immunotherapy, and targeted therapies holds promise for achieving synergistic effects to overcome resistance and improve cancer treatment outcomes.

Keywords:  Cancer metabolism; Cell-to-cell communication; Chemoresistance; Exosomes; Glycolysis

DOI:  https://doi.org/10.1016/j.cytogfr.2023.07.004
Cytokine Growth Factor Rev. 2023 Jul 01. pii: S1359-6101(23)00028-X. [Epub ahead of print]

Exosomes: Another intercellular lipometabolic communication mediators in digestive system neoplasms?

Shaodong Li, Ruizhi Dong, Zhenhua Kang, Hucheng Li, Xueliang Wu, Tian Li.

  Neoplasms are one of the most concerned public health problems worldwide. Digestive system neoplasms, with a high morbidity and mortality, is one of the most common malignant tumors in human being. It is found that exosomes act as an intercellular communication media to carry the metabolic and genetic information of parental cells to target cells. Likely, exosomes participate in lipid metabolism and regulates multiple processes in digestive system neoplasms, including the information transmission among cancer cells, the formation of neoplastic microenvironment, and the neoplastic biological behaviors like metastasis, invasion, and the chemotherapy resistance. In this review, we firstly introduce the main mechanisms whereas exosomes act as intercellular lipometabolic communication mediator in digestive system neoplasms. Thereafter we introduce the relationship between exosomes lipid metabolism and various type of digestive system neoplasms, including gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. Eventually, we summarized and prospected the development and implication of exosomes in digestive system neoplasms. The further research of exosomes as intercellular lipid metabolism mediator will contribute to accurate and efficient diagnosis and treatment of digestive system neoplasms.

Keywords:  Cellular communication; Communication mediator; Digestive system neoplasms; Exosomes; Lipid metabolism

DOI:  https://doi.org/10.1016/j.cytogfr.2023.06.005