bims-exocan 2023-12-10 papers

Issue of 2023–12–10
five papers selected by
Muhammad Rizwan, COMSATS University

Mol Cancer. 2023 Dec 05. 22(1): 197

Significant CircRNAs in liver cancer stem cell exosomes: mediator of malignant propagation in liver cancer?

Tao Han, Lujun Chen, Kerui Li, Qilin Hu, Yue Zhang, Xuan You, Lei Han, Tingsong Chen, Kai Li.

Hepatocellular carcinoma (HCC), one of the most prevalent forms of cancer worldwide, presents a significant global healthcare challenge. Cancer stem cells (CSCs), which can influence neighboring non-CSCs, are believed to play a crucial role in tumor growth and resistance to treatment, but the specific mechanisms and mediators are not fully understood. Regulation of the CSC state is considered an ideal therapeutic strategy both in the early stages of tumor formation and within established tumors. Exosomes have emerged as key players in intercellular communication, similar to classical hormone signaling, and are essential for facilitating communication between cells in liver cancer. Here, by coupling immunomagnetic bead sorting and exosomal sequencing, we found that exosome-derived circRNAs enriched in liver cancer CSCs were the key subsets with stemness characteristics and ultimately promoted HCC development. Of interest, we found that circ-ZEB1 and circ-AFAP1 are strongly correlated with liver cancer stemness and a poor prognosis, and can regulate the epithelial-mesenchymal transition (EMT) process. Our novel exosome-derived circRNAs play a vital role as key components of various intercellular crosstalk and communication systems in malignant transmission. This finding not only provides valuable support for utilizing plasma exosomal circRNAs as clinical prognostic indicators for HCC patients but also highlights a new research direction in exploring the signaling between liver CSCs and the messenger molecules contained within exosomes.

Keywords: Bioinformatics analysis; CD133; Exosomes; Liver cancer stem cells; circRNA

DOI: https://doi.org/10.1186/s12943-023-01891-y

F1000Res. 2023 ;12 58

Exosomes: Mediators of cellular communication in potentially malignant oral lesions and head and neck cancers.

Monica Charlotte Solomon, Chetana Chandrashekar, Spoorti Kulkarni, Nisha Shetty, Aditi Pandey.

Exosomes are a unique type of extracellular vesicles that contain a plethora of biological cargo such as miRNA, mRNA, long non-coding RNA, DNA, proteins and lipids. Exosomes serve as very effective means of intercellular communication. Due the presence of a lipid bilayer membrane, exosomes are resistant to degradation and are highly stable. This makes them easily identifiable in blood and other bodily fluids such as saliva. The exosomes that are secreted from a parent cell directly release their contents into the cytoplasm of a recipient cell and influence their cellular activity and function. Exosomes can also transfer their content between cancer cells and normal cells and regulate the tumor microenvironment. Exosomes play a vital role in tumor growth, tumor invasion and metastasis. Exosomes provide a multitude of molecular and genetic information and have become valuable indicators of disease activity at the cellular level. This review explores the molecular characteristics of exosomes and the role that exosomes play in the tumorigenesis pathway of potentially malignant oral lesions and head and neck cancers The application of exosomes in the treatment of oral cancers is also envisioned. Exosomes are very small and can easily pass through various biological barriers, making them very good delivery vectors for therapeutic drugs as well as to selectively induce DNA's mRNA and miRNAs into targeted cancer cells.

Keywords: Exosomes; intercellular communication; invasion and metastasis; miRNA; tumor microenvironment

DOI: https://doi.org/10.12688/f1000research.127368.2

Am J Cancer Res. 2023 ;13(11): 5368-5381

Exosomes with IR780 and Lenvatinib loaded on GPC3 single-chain scFv antibodies for targeted hyperthermia and chemotherapy in hepatocellular carcinoma therapy.

Shenan Huang, Ming Xiong, Jie Liu, Jian Wang, Xianyang Han, Zhimeng Chen, Peiyi Xie, Zhipeng Zhou, Cong Liu, Hui Li, Zhili Wen, Xiaomei Huang, Binghai Zhou.

Exosomes (EXOs) are considered natural nanoparticles which have been widely used as carriers for the treatment and diagnosis of various diseases. However, due to the non-specific uptake, the unmodified EXOs cannot effectively deliver the vector to the target site. In this study, we used pDisplay vector to engineer Glypican-3 (GPC3) single-chain scFv antibody to the exosome surface, and the effect of engineered exosomes on the proliferation and migration of hepatocellular carcinoma (HCC) cells was determined by a series of in vitro experiments as well as in vivo mouse xenograft model and PDX model. Furthermore, we established an improved delivery system by engineering single-chain scFv antibody against GPC3 on the EXO surface for a more efficient HCC targeting. Moreover, the delivery system was loaded with IR780 and Lenvatinib for a combination of thermotherapy and chemotherapy. Our results revealed that the antibody-engineered exosomes enabled rapid imaging of HCC xenograft models post IR780 loading and showed significant anti-tumor photothermal therapy (PTT) effects after irradiation. Since dual loading of IR780 and Lenvatinib in exosomes required only a single injection and had a maximal efficacy against cancer cells, our findings highlight the clinical application of using GPC3 single-chain scFv antibody-engineered exosomes loaded with IR780 and Lenvartinib to achieve the imaging and the treatment of HCC from the combined effect of IR780-induced PTT and Lenvatinib-induced chemotherapy.

Keywords: GPC3 single chain antibody; IR780; Lenvartinib; exosomes; hepatocellular carcinoma

iScience. 2023 Dec 15. 26(12): 108414

Helicobacter pylori CagA promotes immune evasion of gastric cancer by upregulating PD-L1 level in exosomes.

Jinfeng Wang, Rilin Deng, Shuai Chen, Shun Deng, Qi Hu, Biaoming Xu, Junjun Li, Zhuo He, Mingjing Peng, Sanlin Lei, Tiexiang Ma, Zhuo Chen, Haizhen Zhu, Chaohui Zuo.

Cytotoxin-associated gene A (CagA) of Helicobacter pylori (Hp) may promote immune evasion of Hp-infected gastric cancer (GC), but potential mechanisms are still under explored. In this study, the positive rates of CagA and PD-L1 protein in tumor tissues and the high level of exosomal PD-L1 protein in plasma exosomes were significantly associated with the elevated stages of tumor node metastasis (TNM) in Hp-infected GC. Moreover, the positive rate of CagA was positively correlated with the positive rate of PD-L1 in tumor tissues and the level of PD-L1 protein in plasma exosomes, and high level of exosomal PD-L1 might indicate poor prognosis of Hp-infected GC. Mechanically, CagA increased PD-L1 level in exosomes derived from GC cells by inhibiting p53 and miRNA-34a, suppressing proliferation and anticancer effect of CD8+ T cells. This study provides sights for understanding immune evasion mediated by PD-L1. Targeting CagA and exosomal PD-L1 may improve immunotherapy efficacy of Hp-infected GC.

Keywords: Cancer; Gastroenterology; Microbiology

DOI: https://doi.org/10.1016/j.isci.2023.108414

Nanomedicine (Lond). 2023 Dec 07.

Engineering extracellular vesicles mimetics for targeted chemotherapy of drug-resistant ovary cancer.

Xiaoguang Liu, Guangquan Liu, Yinghua Mao, Jie Luo, Yongping Cao, Weilong Tan, Wenhao Li, Huanhuan Yu, Xuemei Jia, Hong Li.

Aim: To develop nanocarriers for targeting the delivery of chemotherapeutics to overcome multidrug-resistant ovarian cancer. Materials & methods: Doxorubicin-loaded nanovesicles were obtained through serial extrusion, followed by loading of P-glycoprotein siRNA and folic acid. The targeting ability and anticancer efficacy of the nanovesicles were evaluated. Results: The doxorubicin-loaded nanovesicles showed a high production yield. The presence of P-glycoprotein siRNA and folic acid resulted in reversed drug resistance and tumor targeting. This nanoplatform tremendously inhibited the viability of multidrug-resistant ovarian cancer cells, which was able to target tumor tissue and suppress tumor growth without adverse effects. Conclusion: These bioengineered nanovesicles could serve as novel extracellular vesicles mimetics for chemotherapeutics delivery to overcome multidrug resistance.

Keywords: RNAi; drug-delivery system; engineering nanovesicles; extracellular vesicles-mimetics; multidrug resistance; targeting therapy

DOI: https://doi.org/10.2217/nnm-2023-0289