Cancer‑associated fibroblast‑derived exosomal miR‑382‑5p promotes the migration and invasion of oral squamous cell carcinoma

Abstract

Oral squamous cell carcinoma (OSCC), with high potential for metastasis, is the most common malignant tumor of the head and neck. Cancer-associated fibroblasts (CAFs) are the main stromal cells in the microenvironment and aggravate tumor progression. However, whether CAFs are associated with the progression of OSCC remains unknown and the underlying mechanism remains unclear. In the present study, the role of CAFs in mediating OSCC cell migration and invasion was investigated, and the participation of exosomal miR-382-5p in this process was elucidated. In this study, according to the α-SMA staining with immunohistochemistry, 47 OSCC patients were divided into CAFs-rich and CAFs poor groups, and association of CAF density and clinicopathologic features of the OSCC patients were analyzed with Pearson χ 2 test. Transwell assay was used for evaluating cell migration and invasion ability of OSCC cells after being co-cultured with NFs or CAFs, or after added exosomes. qPCR was used to detect the expression of miR-382-5p. Western blot analysis was used to measure the expression of migration and invasion-associated proteins. In the present study, the CAF density in tumor tissues was found to be relevant to OSCC lymph node metastasis and TNM stage. Furthermore, we revealed that miR-382-5p was overexpressed in CAFs compared with that in fibroblasts of adjacent normal tissue and miR-382-5p overexpression was responsible for OSCC cell migration and invasion. Finally, we demonstrated that CAF-derived exosomes transported miR-382-5p to OSCC cells. The present study confirmed a new mechanism of CAF-facilitated OSCC progression and may be beneficial for identifying new cancer therapeutic targets.

Ovatodiolide Suppresses Oral Cancer Malignancy by Down-Regulating Exosomal Mir-21/STAT3/β-Catenin Cargo and Preventing Oncogenic Transformation of Normal Gingival Fibroblasts

“…Furthermore, our data also demonstrated that TGF-β1-containing CSC_EVs possibly participate in the transformation of NGFs into CAFs and might promote their metastatic potential, thereby transforming the TME. This is in part consistent with previous evidence that CAF-secreted EVs facilitate the tumorigenesis of oral cancer cells [36][37][38]. However, the observation that CSC_EVs promoted the transformation of NGFs to CAFs is unique to this study and is the first such documentation, to the best of our knowledge.…”

Cancer‐associated fibroblasts–derived exosomes‐mediated transfer of LINC00355 regulates bladder cancer cell proliferation and invasion

“…Increasing studies have highlighted the important role of exosomes in crosstalk between CAFs and cancer cells via carrying miRNAs, lncRNAs, proteins, metabolites, and other substances . For example, Sun et al found that CAFs exosome promoted oral squamous cell carcinoma (OSCC) cell migration and invasion by transporting miR‐382‐5p to OSCC cells . A recent study demonstrated that activated CAFs can secrete interleukin‐6 (IL‐6) to promote epithelial mesenchymal transformation of BC cells and participate in the regulation of proliferation and migration of BC cells .…”

TGF-Beta-Activated Cancer-Associated Fibroblasts Limit Cetuximab Efficacy in Preclinical Models of Head and Neck Cancer

“…TGF-beta plays a crucial role in TME, mediating both immunosuppression and inducing epithelial-mesenchymal transition (EMT) [43,44], and is known to be secreted by CAFs (Reviewed in [45,46]). CAFs are an important component in the TME that play a pivotal role in tumor cell proliferation, invasion, and metastasis in multiple cancer types [47][48][49][50] including HNC [51,52]. CAFs are also known to confer resistance to anti-EGFR therapies among different cancer types including colon [53], lung [54][55][56], breast [57], and in HNC.…”