ABSTRACT
BACKGROUND: Cancer associated fibroblasts (CAFs) can remodel tumor microenvironment by secreting exosomes. This study aimed to investigate the role of exosomes derived from cancer-associated fibroblasts in colorectal cancer (CRC) progression. METHODS: Circular RNA (circRNA) array was used to identify differentially expressed circRNAs in exosomes from normal fibroblasts (NFs) and CAFs, and confirmed one differentially expressed circRNA circ_0067557 by real-time PCR. The effect of circ_0067557 on proliferation, metastasis, chemoresistance and apoptosis was verified by wound heal, tranwell, CCK8, sphere-forming and flow cytometry assay. RESULTS: Circ_0067557 expression in exosomes from CAFs was higher than those from NFs. CAF-derived exosomes promoted the proliferation, migration, invasion and chemoresistance of CRC cells while suppressed apoptosis. Silencing of circ_0067557 inhibited malignant phenotypes of CRC cells by targeting Lin28A and Lin28B. Moreover, CAF-derived exosomes enhanced the growth of CRC xenograft tumors. CONCLUSION: Circ_0067557/Lin28A and Lin28B signal axis may be a potential therapy target for CRC.
Subject(s)
Cancer-Associated Fibroblasts , Colorectal Neoplasms , Exosomes , MicroRNAs , Humans , Cancer-Associated Fibroblasts/metabolism , Carcinogenesis/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Cell Transformation, Neoplastic/metabolism , Colorectal Neoplasms/pathology , Drug Resistance, Neoplasm/genetics , Exosomes/genetics , Exosomes/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Circular/genetics , RNA, Circular/metabolism , Tumor Microenvironment/genetics , AnimalsABSTRACT
The occurrence and progression of tumors can be established through a complex interplay among tumor cells undergoing epithelial-mesenchymal transition (EMT), invasive factors and immune cells. In this study, we employed single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (ST) to evaluate the pseudotime trajectory and spatial interactive relationship between EMT-invasive malignant tumors and immune cells in primary colorectal cancer (CRC) tissues at different stages (stage I/II and stage III with tumor deposit). Our research characterized the spatiotemporal relationship among different invasive tumor programs by constructing pseudotime endpoint-EMT-invasion tumor programs (EMTPs) located at the edge of ST, utilizing evolution trajectory analysis integrated with EMT-invasion genes. Strikingly, the invasive and expansive process of tumors undergoes remarkable spatial reprogramming of regulatory and immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), regulatory T cells (Treg), and exhausted T cells (Tex). These EMTP-adjacent cell are linked to EMT-related invasion genes, especially the C-X-C motif ligand 1 (CXCL1) and CXCL8 genes that are important for CRC prognosis. Interestingly, the EMTPs in stage I mainly produce an inflammatory margin invasive niche, while the EMTPs in stage III tissues likely produce a hypoxic pre-invasive niche. Our data demonstrate the crucial role of regulatory and immunosuppressive cells in tumor formation and progression of CRC. This study provides a framework to delineate the spatiotemporal invasive niche in CRC samples.
Subject(s)
Colorectal Neoplasms , Epithelial-Mesenchymal Transition , Humans , Epithelial-Mesenchymal Transition/genetics , Colorectal Neoplasms/pathology , Prognosis , Biomarkers, Tumor/genetics , Cell Line, Tumor , Tumor MicroenvironmentABSTRACT
[This corrects the article DOI: 10.3389/fmolb.2022.881794.].
ABSTRACT
Head and neck squamous cell carcinoma (HNSCC), originating from the mucosal epithelial cells of the oral cavity, pharynx, and larynx, is a lethal malignancy of the head and neck. Patients with advanced and recurrent HNSCC have poor outcomes due to limited therapeutic options. Exosomes have active roles in the pathophysiology of tumors and are suggested as a potential therapeutic target of HNSCC. Exosomes in HNSCC have been intensively studied for disease activity, tumor staging, immunosuppression, and therapeutic monitoring. In this review, the biological mechanisms and the recent clinical application of exosomes are highlighted to reveal the potential of exosomes as biomarkers and therapeutic targets for HNSCC.
