bims-exocan 2023-11-26 papers

Issue of 2023–11–26
five papers selected by
Muhammad Rizwan, COMSATS University

Biomark Res. 2023 Nov 19. 11(1): 100

Exosome derived from tumor-associated macrophages: biogenesis, functions, and therapeutic implications in human cancers.

Manli Zhou, Xiaoyun He, Cheng Mei, Chunlin Ou.

Tumor-associated macrophages (TAMs), one of the most abundant immune cell types in the tumor microenvironment (TME), account for approximately 50% of the local hematopoietic cells. TAMs play an important role in tumorigenesis and tumor development through crosstalk between various immune cells and cytokines in the TME. Exosomes are small extracellular vesicles with a diameter of 50-150 nm, that can transfer biological information (e.g., proteins, nucleic acids, and lipids) from secretory cells to recipient cells through the circulatory system, thereby influencing the progression of various human diseases, including cancer. Recent studies have suggested that TAMs-derived exosomes play crucial roles in malignant cell proliferation, invasion, metastasis, angiogenesis, immune responses, drug resistance, and tumor metabolic reprogramming. TAMs-derived exosomes have the potential to be targeted for tumor therapy. In addition, the abnormal expression of non-coding RNAs and proteins in TAMs-derived exosomes is closely related to the clinicopathological features of patients with cancer, and these exosomes are expected to become new liquid biopsy markers for the early diagnosis, prognosis, and monitoring of tumors. In this review, we explored the role of TAMs-derived exosomes in tumorigenesis to provide new diagnostic biomarkers and therapeutic targets for cancer prevention.

Keywords: Exosomes; Liquid biopsy; Metabolic reprogramming; Therapeutic target; Tumor microenvironment; Tumor-associated macrophages

DOI: https://doi.org/10.1186/s40364-023-00538-w

Biomolecules. 2023 Oct 25. pii: 1574. [Epub ahead of print]13(11):

The Role of Exosome-Derived microRNA on Lung Cancer Metastasis Progression.

Israel Martinez-Espinosa, José Antonio Serrato, Blanca Ortiz-Quintero.

The high mortality from lung cancer is mainly attributed to the presence of metastases at the time of diagnosis. Despite being the leading cause of lung cancer death, the underlying molecular mechanisms driving metastasis progression are still not fully understood. Recent studies suggest that tumor cell exosomes play a significant role in tumor progression through intercellular communication between tumor cells, the microenvironment, and distant organs. Furthermore, evidence shows that exosomes release biologically active components to distant sites and organs, which direct metastasis by preparing metastatic pre-niche and stimulating tumorigenesis. As a result, identifying the active components of exosome cargo has become a critical area of research in recent years. Among these components are microRNAs, which are associated with tumor progression and metastasis in lung cancer. Although research into exosome-derived microRNA (exosomal miRNAs) is still in its early stages, it holds promise as a potential target for lung cancer therapy. Understanding how exosomal microRNAs promote metastasis will provide evidence for developing new targeted treatments. This review summarizes current research on exosomal miRNAs' role in metastasis progression mechanisms, focusing on lung cancer.

Keywords: exosome; lung cancer; metastasis; microRNA

DOI: https://doi.org/10.3390/biom13111574

J Gastroenterol Hepatol. 2023 Nov 20.

Exosomal-miR-522-3p derived from cancer-associated fibroblasts accelerates tumor metastasis and angiogenesis via repression bone morphogenetic protein 5 in colorectal cancer.

Jun Zhang, Yuliang Pan, Long Jin, Huiyun Yang, Peiguo Cao.

BACKGROUND: Colorectal cancer (CRC) is a gastrointestinal tract malignancy. Exosomes secreted by cancer-associated fibroblasts (CAFs) are reported to participate in tumor progression by delivering noncoding RNA or small proteins. However, the function of exosomal miR-522-3p in CRC remains unclear.
METHODS: CAFs were derived from tumor tissues, and exosomes were identified by western blot or TEM/NTA and originated from CAFs/NFs. The viability, invasion, and migration of HUVECs and CRC cells was examined using MTT, Transwell, and wound healing assays, respectively. The molecular interactions were validated using dual luciferase reporter assay and RIP. Xenograft and lung metastasis mouse models were generated to assess tumor growth and metastasis.
RESULTS: Exosomes extracted from CAFs/NFs showed high expression of CD63, CD81, and TSG101. CAF-derived exosomes significantly increased the viability, angiogenesis, invasion, and migration of HUVECs and CRC cells, thereby aggravating tumor growth, invasion, and angiogenesis in vivo. miR-522-3p was upregulated in CAF-derived exosomes and CRC tissues. Depletion of miR-522-3p reversed the effect of exosomes derived from CAFs in migration, angiogenesis, and invasion of HUVECs and CRC cells. Furthermore, bone morphogenetic protein 5 (BMP5) was identified as a target gene of miR-522-3p, and upregulation of BMP5 reversed the promoting effect of miR-522-3p mimics or CAF-derived exosomes on cell invasion, migration, and angiogenesis of HUVECs and CRC cells.
CONCLUSION: Exosomal miR-522-3p from CAFs promoted the growth and metastasis of CRC through downregulating BMP5, which might provide new strategies for the treatment of CRC.

Keywords: BMP5; CAFs-exos; CRC; miR-522-3p

DOI: https://doi.org/10.1111/jgh.16345

Cancer Cell Int. 2023 Nov 21. 23(1): 287

Tumor-derived exosomal linc00881 induces lung fibroblast activation and promotes osteosarcoma lung migration.

Xinyu Chang, Qiuyu Tan, Jinwen Xu, Xu Wu, Ying Wang, Yuan Zhang, Hao Zhang, Haijun Liu, Liang Yan.

Osteosarcoma (OS) commonly metastasizes to the lung, yet the underlying molecular mechanisms remain poorly understood. Exosomes play a crucial role in tumor migration, including OS lung migration. However, the underlying mechanism by which exosome-derived long non-coding RNAs (lncRNAs) contribute to lung migration in osteosarcoma (OS) remains unclear. This study presents a newly discovered lncRNA, linc00881, derived from OS exosomes. Our study shows that linc00881 promotes the migration of OS cells to the lung and induces the conversion of normal lung fibroblasts into cancer-associated fibroblasts (CAFs). Subsequently, we found that exosomal linc00881 secreted by OS cells can regulate the expression of matrix metalloproteinase 2 (MMP2) in HFL-1 cells by sponging miR-29c-3p, thereby activating the NF-κB signaling in lung fibroblasts. Finally, we discovered that pro-inflammatory cytokines, namely IL-1β, IL-6, and IL-8, were secreted through the linc00881/miR-29c-3p/MMP2 axis. These results suggest that OS-derived exosomes can mediate the intercellular crosstalk between OS cells and lung fibroblasts, ultimately impacting OS lung migration. Our study provides a potential target for the treatment of OS lung migration.

Keywords: Lung fibroblast activation; Lung migration; MMP2; Osteosarcoma; linc00881

DOI: https://doi.org/10.1186/s12935-023-03121-3

Sci Adv. 2023 Nov 24. 9(47): eadk1098

Patient-derived exosomes facilitate therapeutic targeting of oncogenic MET in advanced gastric cancer.

Sujin Hyung, Jihoon Ko, You Jeong Heo, Steven M Blum, Seung Tae Kim, Se Hoon Park, Joon Oh Park, Won Ki Kang, Ho Yeong Lim, Samuel J Klempner, Jeeyun Lee.

Gastric cancer (GC) with peritoneal metastases and malignant ascites continues to have poor prognosis. Exosomes mediate intercellular communication during cancer progression and promote therapeutic resistance. Here, we report the significance of exosomes derived from malignant ascites (EXOAscites) in cancer progression and use modified exosomes as resources for cancer therapy. EXOAscites from patients with GC stimulated invasiveness and angiogenesis in an ex vivo three-dimensional autologous tumor spheroid microfluidic system. EXOAscites concentration increased invasiveness, and blockade of their secretion suppressed tumor progression. In MET-amplified GC, EXOAscites contain abundant MET; their selective delivery to tumor cells enhanced angiogenesis and invasiveness. Exosomal MET depletion substantially reduced invasiveness; an additive therapeutic effect was induced when combined with MET and/or VEGFR2 inhibition in a patient-derived MET-amplified GC model. Allogeneic MET-harboring exosome delivery induced invasion and angiogenesis in a MET non-amplified GC model. MET-amplified patient tissues showed higher exosome concentration than their adjacent normal tissues. Manipulating exosome content and production may be a promising complementary strategy against GC.

DOI: https://doi.org/10.1126/sciadv.adk1098