TGF-B-induced Cancer-associated Fibroblast Activation Promotes Tumor Progression In Oral Squamous Cell Carcinoma...

Oral squamous cell carcinoma (OSCC) is a common malignancy with a poor prognosis, partly due to interactions within the tumor microenvironment. Cancer-associated fibroblasts (CAFs), key stromal components, promote tumor progression by enhancing cancer cell migration, angiogenesis, and extracellular matrix remodeling. Transforming growth factor-beta (TGF-β) is known to induce CAF differentiation from normal fibroblasts (NFs), but its functional contribution in OSCC remains to be fully elucidated. This study explored the role of TGF-β in inducing the transition of NFs into CAFs and its impact on progression of OSCC.

In vitro, NFs were treated with TGF-β, and CAF induction was assessed by evaluating the expression of the CAF marker α-smooth muscle actin (α-SMA) using quantitative real-time PCR and fluorescent immunostaining. OSCC cell migration was analyzed using a scratch assay. In vivo, TGF-β-treated or untreated NFs were co-injected with OSCC cells. The tumor size and VEGF, MMP2, and MMP9 expression were analyzed via quantitative real-time PCR and immunohistochemistry.

In vitro, TGF-β-treated NFs exhibited significantly increased α-SMA expression and enhanced the OSCC migratory ability. In vivo, the TGF-β-treated group demonstrated a marked increase in tumor growth and up-regulated expression of VEGF, MMP2, and MMP9 compared to the untreated group.

These findings suggest that TGF-β induces CAF differentiation and facilitates tumor progression by promoting angiogenesis and extracellular matrix degradation. This study highlights the potential of targeting TGF-β as a therapeutic strategy and underscores the need for novel approaches to counteract the tumor-promoting effects of CAFs.