bims-exocan 2023-12-24 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2023–12–24
eight papers selected by
Muhammad Rizwan, COMSATS University

Exosomal Cargo in Ovarian Cancer Dissemination.
Engineered exosomes: a promising vehicle in cancer therapy.
Role of Exosomes in Epithelial-Mesenchymal Transition.
Extracellular vesicles in the breast cancer brain metastasis: physiological functions and clinical applications.
Lung Cancer Cell-Derived Exosome Detection Using Electrochemical Approach towards Early Cancer Screening.
Pancreatic cancer stem cell-derived exosomal miR-210 mediates macrophage M2 polarization and promotes gemcitabine resistance by targeting FGFRL1.
Effective exosomes in breast cancer: focusing on diagnosis and treatment of cancer progression.
Tumor-Derived Exosomal LINC01480 Upregulates VCAM1 Expression by Acting as a Competitive Endogenous RNA of miR-204-5p to Promote Gastric Cancer Progression.

Curr Issues Mol Biol. 2023 Dec 07. 45(12): 9851-9867

Exosomal Cargo in Ovarian Cancer Dissemination.

Ekaterina Dzhugashvili, Svetlana Tamkovich.

  Ovarian cancer (OC) has the highest mortality rate among all gynecologic cancers and is characterized by early peritoneal spread. The growth and development of OC are associated with the formation of ascitic fluid, creating a unique tumor microenvironment. Understanding the mechanisms of tumor progression is crucial in identifying new diagnostic biomarkers and developing novel therapeutic strategies. Exosomes, lipid bilayer vesicles measuring 30-150 nm in size, are known to establish a crucial link between malignant cells and their microenvironment. Additionally, the confirmed involvement of exosomes in carcinogenesis enables them to mediate the invasion, migration, metastasis, and angiogenesis of tumor cells. Functionally active non-coding RNAs (such as microRNAs, long non-coding RNAs, circRNAs), proteins, and lipid rafts transported within exosomes can activate numerous signaling pathways and modify gene expression. This review aims to expand our understanding of the role of exosomes and their contents in OC carcinogenesis processes such as epithelial-mesenchymal transition (EMT), angiogenesis, vasculogenic mimicry, tumor cell proliferation, and peritoneal spread. It also discusses the potential for utilizing exosomal cargo to develop novel "liquid biopsy" biomarkers for early OC diagnosis.

Keywords:  exosomal cargo; exosomes; liquid biopsy; microRNA; ovarian cancer; proteins

DOI:  https://doi.org/10.3390/cimb45120615
Ther Deliv. 2023 Dec;14(12): 775-794

Engineered exosomes: a promising vehicle in cancer therapy.

Farkhondeh Pooresmaeil, Sahar Andi, Behnam Hasannejad-Asl, Shahla Takamoli, Azam Bolhassani.

  During the past few decades, researchers have attempted to discover an effective treatment for cancer. Exosomes are natural nanovesicles released by various cells and play a role in communication between cells. While natural exosomes have high clinical potential, their inherent limitations have prompted researchers to design exosomes with improved therapeutic properties. To achieve this purpose, researchers have undertaken exosome engineering to modify the surface properties or internal composition of exosomes. After these modifications, engineered exosomes can be used as carriers for delivery of chemotherapeutic agents, targeted drug delivery or development of cancer vaccines. The present study provides an overview of exosomes, including their biogenesis, biological functions, isolation techniques, engineering methods, and potential applications in cancer therapy.

Keywords:  biological function; cancer therapy; carrier; engineered exosomes; vaccine

DOI:  https://doi.org/10.4155/tde-2023-0131
ACS Appl Bio Mater. 2023 Dec 18.

Role of Exosomes in Epithelial-Mesenchymal Transition.

Bikramjit Bhattacharya, Sagnik Nag, Sayantanee Mukherjee, Mrunal Kulkarni, Priti Chandane, Debashmita Mandal, Nobendu Mukerjee, Divya Mirgh, Krishnan Anand, Manab Deb Adhikari, Sukhamoy Gorai, Nanasaheb Thorat.

  Epithelial-mesenchymal transition (EMT) is a fundamental process driving cancer metastasis, transforming non-motile cells into a motile population that migrates to distant organs and forms secondary tumors. In recent years, cancer research has revealed a strong connection between exosomes and the EMT. Exosomes, a subpopulation of extracellular vesicles, facilitate cellular communication and dynamically regulate various aspects of cancer metastasis, including immune cell suppression, extracellular matrix remodeling, metastasis initiation, EMT initiation, and organ-specific metastasis. Tumor-derived exosomes (TEXs) and their molecular cargo, comprising proteins, lipids, nucleic acids, and carbohydrates, are essential components that promote EMT in cancer. TEXs miRNAs play a crucial role in reprogramming the tumor microenvironment, while TEX surface integrins contribute to organ-specific metastasis. Exosome-based cancer metastasis research offers a deeper understanding about cancer and an effective theranostic platform development. Additionally, various therapeutic sources of exosomes are paving the way for innovative cancer treatment development. In this Review, we spotlight the role of exosomes in EMT and their theranostic impact, aiming to inspire cancer researchers worldwide to explore this fascinating field in more innovative ways.

Keywords:  Biomarkers; Cancer; EMT; Exosome; Metastasis; Therapeutic

DOI:  https://doi.org/10.1021/acsabm.3c00941
Front Hum Neurosci. 2023 ;17 1278501

Extracellular vesicles in the breast cancer brain metastasis: physiological functions and clinical applications.

Yuima Sakamoto, Takahiro Ochiya, Yusuke Yoshioka.

  Breast cancer, which exhibits an increasing incidence and high mortality rate among cancers, is predominantly attributed to metastatic malignancies. Brain metastasis, in particular, significantly contributes to the elevated mortality in breast cancer patients. Extracellular vesicles (EVs) are small lipid bilayer vesicles secreted by various cells that contain biomolecules such as nucleic acids and proteins. They deliver these bioactive molecules to recipient cells, thereby regulating signal transduction and protein expression levels. The relationship between breast cancer metastasis and EVs has been extensively investigated. In this review, we focus on the molecular mechanisms by which EVs promote brain metastasis in breast cancer. Additionally, we discuss the potential of EV-associated molecules as therapeutic targets and their relevance as early diagnostic markers for breast cancer brain metastasis.

Keywords:  biomarker; blood-brain barrier (BBB); breast cancer brain metastases; exosomes; extracellular vesicles (EVs)

DOI:  https://doi.org/10.3389/fnhum.2023.1278501
Int J Mol Sci. 2023 Dec 07. pii: 17225. [Epub ahead of print]24(24):

Lung Cancer Cell-Derived Exosome Detection Using Electrochemical Approach towards Early Cancer Screening.

Koosha Irani, Hossein Siampour, Abdollah Allahverdi, Ahmad Moshaii, Hossein Naderi-Manesh.

  Lung cancer is one of the deadliest cancers worldwide due to the inability of existing methods for early diagnosis. Tumor-derived exosomes are nano-scale vesicles released from tumor cells to the extracellular environment, and their investigation can be very useful in both biomarkers for early cancer screening and treatment assessment. This research detected the exosomes via an ultrasensitive electrochemical biosensor containing gold nano-islands (Au-NIs) structures. This way, a high surface-area-to-volume ratio of nanostructures was embellished on the FTO electrodes to increase the chance of immobilizing the CD-151 antibody. In this way, a layer of gold was first deposited on the electrode by physical vapor deposition (PVD), followed by thermal annealing to construct primary gold seeds on the surface of the electrode. Then, gold seeds were grown by electrochemical deposition through gold salt. The cell-derived exosomes were successfully immobilized on the FTO electrode through the CD-151 antibody, and cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) methods were used in this research. In the CV method, the change in the current passing through the working electrode is measured so that the connection of exosomes causes the current to decrease. In the EIS method, surface resistance changes were investigated so that the binding of exosomes increased the surface resistance. Various concentrations of exosomes in both cell culture and blood serum samples were measured to test the sensitivity of the biosensor, which makes our biosensor capable of detecting 20 exosomes per milliliter.

Keywords:  A549 cell line; early lung cancer diagnosis; electrochemical biosensor; exosomes

DOI:  https://doi.org/10.3390/ijms242417225
Int Immunopharmacol. 2023 Dec 21. pii: S1567-5769(23)01734-4. [Epub ahead of print]127 111407

Pancreatic cancer stem cell-derived exosomal miR-210 mediates macrophage M2 polarization and promotes gemcitabine resistance by targeting FGFRL1.

Yao Guo, Jing Cui, Xueyi Liang, Taoyu Chen, Chong Lu, Tao Peng.

  Pancreatic cancer (PC) is a serious threat to human health, with most patients diagnosed at the advanced stages of the disease. Treatment with gemcitabine (GEM) leads to PC GEM resistance. In addition, cancer stem cell (CSC)-derived exosomes play an important role in cancer progression. We aimed to investigate the role and mechanism of action of PC stem cell-derived exosomes in PC drug resistance and progression. CSC-derived exosomes increased the proportion of F4/80+/CD86 + cells and levels of M2 polarization factors. miR-210 is expressed in CSC-derived exosomes. Thus, following co-culture, miR-210 was taken up by macrophages. Transfection or the addition of miR-210 mimics increased the proportion of F4/80+/CD206 + cells and levels of M2 polarization factors. Further, the miR-210 targets inhibited the levels of FGFRL1. The FGFRL1 overexpression plasmid also inhibited miR-210-mediated M2 polarization. After co-culture of THP-M2 cells with PC cells and treatment with GEM, the survival rate, migration rate, and levels of MDR, YB-1, BCRP, p-PI3K, p-AKT, and p-mTOR in PC cells increased. And THP-M2 increased the tumor volume and MDR, YB-1, BCRP, p-PI3K, p-AKT, and p-mTOR levels. Overall, miR-210 from PC stem cell-derived exosome targets and inhibits FGFRL1 to promote macrophage M2 polarization, which activates the p-PI3K/p-AKT/p-mTOR pathway and increases GEM resistance.

Keywords:  Gemcitabine resistance; Pancreatic cancer; Stem cell-derived exosomal; macrophage M2 polarization; miR-210

DOI:  https://doi.org/10.1016/j.intimp.2023.111407
Pathol Res Pract. 2023 Nov 29. pii: S0344-0338(23)00696-9. [Epub ahead of print]253 154995

Effective exosomes in breast cancer: focusing on diagnosis and treatment of cancer progression.

Bekhzod Abdullaev, Sri Anggarini Rasyid, Eyhab Ali, Aiman Mohammed Baqir Al-Dhalimy, Yasser Fakri Mustafa, Mohammed N Fenjan, Neeti Misra, Sada Ghalib Al-Musawi, Ahmed Alawadi, Ali Alsalamy.

  Breast cancer (BC) is the most prevalent aggressive malignant tumor in women worldwide and develops from breast tissue. Although cutting-edge treatment methods have been used and current mortality rates have decreased, BC control is still not satisfactory. Clarifying the underlying molecular mechanisms will help clinical options. Extracellular vesicles known as exosomes mediate cellular communication by delivering a variety of biomolecules, including proteins, oncogenes, oncomiRs, and even pharmacological substances. These transferable bioactive molecules can alter the transcriptome of target cells and affect signaling pathways that are related to tumors. Numerous studies have linked exosomes to BC biology, including therapeutic resistance and the local microenvironment. Exosomes' roles in tumor treatment resistance, invasion, and BC metastasis are the main topics of discussion in this review.

Keywords:  Breast cancer; Exosomes; OncomiRs

DOI:  https://doi.org/10.1016/j.prp.2023.154995
ACS Biomater Sci Eng. 2023 Dec 22.

Tumor-Derived Exosomal LINC01480 Upregulates VCAM1 Expression by Acting as a Competitive Endogenous RNA of miR-204-5p to Promote Gastric Cancer Progression.

Yu Zhang, Shan Guo, Tao Mao, Jing Guo, Qi Zhang, Zibin Tian, Xiaoyu Li.

  Exosomes are a type of cell-derived vesicles that range in size from 30 to 100 nm. They are widely present in various organisms and participate in diverse biological processes, playing crucial roles in tumorigenesis and progression. This study aimed to investigate whether LINC01480 in tumor-derived exosomes is involved in the molecular mechanism of gastric cancer by competitively upregulating the VCAM1 expression through binding miR-204-5p. The study analyzed transcriptome data related to gastric cancer from the cancer genome atlas database and constructed a risk-scoring model for epithelial-mesenchymal transition (EMT)-related lncRNAs to identify eight EMT-related lncRNAs associated with prognosis. EMT-related mRNAs positively correlated with LINC01480 were screened in the ExoRBase database. In vitro cell experiments showed that exosomal LINC01480 can promote the proliferation, migration, invasion, and EMT of gastric cancer cells by upregulating VCAM1 expression through competitive binding with miR-204-5p. In vivo experiments on nude mice showed that exosomal LINC01480 promotes the development of gastric cancer. These results suggest that exosomal LINC01480 could be a potential therapeutic target for gastric cancer.

Keywords:  LINC01480; VCAM1; epithelial−mesenchymal transition; exosomes; gastric cancer; microRNA-204-5p

DOI:  https://doi.org/10.1021/acsbiomaterials.3c00394