bims-exocan 2024-09-15 papers

Issue of 2024–09–15
five papers selected by
Muhammad Rizwan, COMSATS University

MedComm (2020). 2024 Sep;5(9): e709

Tumor-associated exosomes in cancer progression and therapeutic targets.

Xiaomin Liu, Fan Wu, Wei Pan, Guangchao Liu, Hui Zhang, Dawei Yan, Saijing Zheng, Zhongliang Ma, Xiaojun Ren.

Exosomes are small membrane vesicles that are released by cells into the extracellular environment. Tumor-associated exosomes (TAEs) are extracellular vesicles that play a significant role in cancer progression by mediating intercellular communication and contributing to various hallmarks of cancer. These vesicles carry a cargo of proteins, lipids, nucleic acids, and other biomolecules that can be transferred to recipient cells, modifying their behavior and promoting tumor growth, angiogenesis, immune modulation, and drug resistance. Several potential therapeutic targets within the TAEs cargo have been identified, including oncogenic proteins, miRNAs, tumor-associated antigens, immune checkpoint proteins, drug resistance proteins, and tissue factor. In this review, we will systematically summarize the biogenesis, composition, and function of TAEs in cancer progression and highlight potential therapeutic targets. Considering the complexity of exosome-mediated signaling and the pleiotropic effects of exosome cargoes has challenge in developing effective therapeutic strategies. Further research is needed to fully understand the role of TAEs in cancer and to develop effective therapies that target them. In particular, the development of strategies to block TAEs release, target TAEs cargo, inhibit TAEs uptake, and modulate TAEs content could provide novel approaches to cancer treatment.

Keywords: cancer progression; regulation; therapeutic targets; tumor‐associated exosomes

DOI: https://doi.org/10.1002/mco2.709

Cell Signal. 2024 Sep 10. pii: S0898-6568(24)00366-8. [Epub ahead of print] 111398

Proangiogenic potential of plasma exosomes from prostate cancer patients.

Chao Wang, Chuan Zhou, Dong Wang, Yun-Feng Zhang, Hao-Xuan Lv, Han He, Yong-Qi Ren, Jia Wang, Feng-Hai Zhou.

Angiogenesis plays a pivotal role in the progression and metastasis of solid cancers, including prostate cancer (PCa). While small extracellular vesicles derived from PCa cell lines induce a proangiogenic phenotype in vascular endothelial cells, the contribution of plasma exosomes from patients with PCa to this process remains unclear. Here, we successfully extracted and characterized plasma exosomes. Notably, a ring of PKH67-labeled exosomes was observed around the HUVEC nucleus using fluorescence microscopy, indicating the uptake of exosomes by HUVEC. At the cellular level, PCa plasma exosomes enhanced angiogenesis, proliferation, invasion, and migration of HUVEC cells. Moreover, PCa plasma exosomes promoted angiogenesis and aortic sprouting. MicroRNAs are the most common genetic material in exosomes, and to identify miRNAs associated with the angiogenic response, we performed small RNA sequencing followed by RT-qPCR and bioinformatics analysis. These analyses revealed distinct miRNA profiles in plasma exosomes from patients with PCa compared to healthy individuals. Notably, hsa-miR-184 emerged as a potential regulator implicated in the proangiogenic effects of PCa plasma exosomes.

Keywords: Angiogenesis; Exosomes; Hsa-miR-184; Prostate cancer

DOI: https://doi.org/10.1016/j.cellsig.2024.111398

Int J Biol Sci. 2024 ;20(11): 4341-4363

Exosomal SLC16A1-AS1-induced M2 macrophages polarization facilitates hepatocellular carcinoma progression.

Yuhang Hu, Yang Li, Hewei Xiong, Ya Zhang, Fan Wang, Wenfeng Zhuo, Zhu Zeng, Yong Zhao, Hongda Wang, Ping Hu, Shengbo Han, Yan Huang, Guozheng Lv, Gang Zhao.

Macrophages are the most abundant alternative immune cells in the tumor microenvironment (TME). The cross-talk between macrophages and tumor cells provides an important shelter for the occurrence and development of tumors. As an important information transfer medium, exosomes play an important role in intercellular communication. Nonetheless, how exosomal lncRNAs coordinate the communication between tumor cells and immune cells in hepatocellular carcinoma (HCC) is incompletely understood. We found that HCC exosomes-derived antisense RNA of SLC16A1(SLC16A1-AS1) promoted the malignant progression of HCC by regulating macrophage M2-type polarization. Mechanistically, the HCC exosomal SLC16A1-AS1 enhanced mRNA stabilization of SLC16A1 in macrophage by promoting the interaction between 3' untranslated regions (3'UTR) of SLC16A1 mRNA and heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1). As a lactate transporter, SLC16A1 accelerated lactate influx and then activated c-Raf/ERK signaling to induce M2 polarization of macrophages. Reciprocally, M2 macrophages secreted IL-6 to activate STAT3 and then induce METTL3 transcription in HCC cells, which increasing m6A methylation and stabilization of SLC16A1-AS1. In turn, the reciprocal SLC16A1-AS1/IL-6 signaling between HCC cells and M2 macrophages promoted the proliferation, invasion and glycolysis of HCC cells. Our study highlights that exosomal SLC16A1-AS1 acts as a signaling message that induces lactate-mediated M2 polarization of macrophages, and implies that SLC16A1-AS1 might be an applicable target for therapeutic treatment of HCC.

Keywords: M2 polarization; SLC16A1-AS1; exosomes; m6A; macrophages

DOI: https://doi.org/10.7150/ijbs.94440

Cells. 2024 Aug 26. pii: 1428. [Epub ahead of print]13(17):

Roles of M1 Macrophages and Their Extracellular Vesicles in Cancer Therapy.

Wenli Zhou, Fengtang Yang, Xiuzhen Zhang.

Tumor-associated macrophages (TAMs) are inflammatory cells that are important components of the tumor microenvironment. TAMs are functionally heterogeneous and divided into two main subpopulations with distinct and opposite functions: M1 and M2 macrophages. The secretory function of TAMs is essential for combating infections, regulating immune responses, and promoting tissue repair. Extracellular vesicles (EVs) are nanovesicles that are secreted by cells. They play a crucial role in mediating intercellular information transfer between cells. EVs can be secreted by almost all types of cells, and they contain proteins, microRNAs, mRNAs, and even long non-coding RNAs (lncRNAs) that have been retained from the parental cell through the process of biogenesis. EVs can influence the function and behavior of target cells by delivering their contents, thus reflecting, to some extent, the characteristics of their parental cells. Here, we provide an overview of the role of M1 macrophages and their EVs in cancer therapy by exploring the impact of M1 macrophage-derived EVs (M1-EVs) on tumors by transferring small microRNAs. Additionally, we discuss the potential of M1-EVs as drug carriers and the possibility of reprogramming M2 macrophages into M1 macrophages for disease treatment. We propose that M1-EVs play a crucial role in cancer therapy by transferring microRNAs and loading them with drugs. Reprogramming M2 macrophages into M1 macrophages holds great promise in the treatment of cancers.

Keywords: M1 macrophage; M2 macrophage; cancer; exosome; extracellular vesicles

DOI: https://doi.org/10.3390/cells13171428

BMC Cancer. 2024 Sep 13. 24(1): 1144

Exosomal transcript cargo and functional correlation with HNSCC patients' survival.

Joni Yadav, Apoorva Chaudhary, Tanya Tripathi, Divya Janjua, Udit Joshi, Nikita Aggarwal, Arun Chhokar, Chetkar Chandra Keshavam, Anna Senrung, Alok Chandra Bharti.

BACKGROUND: HPV status in a subset of HNSCC is linked with distinct treatment outcomes. Present investigation aims to elucidate the distinct clinicopathological features of HPV-positive and HPV-negative HNSCC and investigate their association with the HNSCC patient survival.
MATERIALS AND METHODS: The total RNA of exosomes from HPV-positive (93VU147T) and HPV-negative (OCT-1) HNSCC cells was isolated, and the transcripts were estimated using Illumina HiSeq X. The expression of altered transcripts and their clinical relevance were further analyzed using publicly available cancer transcriptome data from The Cancer Genome Atlas (TCGA).
RESULTS: Transcriptomic analyses identified 3785 differentially exported transcripts (DETs) in HPV-positive exosomes compared to HPV-negative exosomes. DETs that regulate the protein machinery, cellular redox potential, and various neurological disorder-related pathways were over-represented in HPV-positive exosomes. TCGA database revealed the clinical relevance of altered transcripts. Among commonly exported abundant transcripts, SGK1 and MAD1L1 showed high expression, which has been correlated with poor survival in HNSCC patients. In the top 20 DETs of HPV-negative exosomes, high expression of FADS3, SGK3, and TESK2 correlated with poor survival of the HNSCC patients in the TCGA database.
CONCLUSION: Overall, our study demonstrates that HPV-positive and HPV-negative cells' exosomes carried differential transcripts cargo that may be related to pathways associated with neurological disorders. Additionally, the altered transcripts identified have clinical relevance, correlating with patient survival in HNSCC, thereby highlighting their potential as biomarkers and as therapeutic targets.

Keywords: Differentially exported transcripts (DETs); Exosomes; Head and neck cancers (HNCs); Human papillomavirus (HPV); Illumina HiSeq; The Cancer Genome Atlas (TCGA)

DOI: https://doi.org/10.1186/s12885-024-12759-9