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

Area of Science:

• Oncology
• Cell Biology
• Cancer Microenvironment Research

Background:

• Oral squamous cell carcinoma (OSCC) has a poor prognosis, influenced by tumor microenvironment interactions.
• Cancer-associated fibroblasts (CAFs) within the stroma promote OSCC progression via migration, angiogenesis, and matrix remodeling.
• Transforming growth factor-beta (TGF-β) is implicated in fibroblast to CAF differentiation, but its specific role in OSCC requires further investigation.

Purpose of the Study:

• To investigate the role of TGF-β in inducing normal fibroblast (NF) to CAF transition.
• To determine the impact of TGF-β-induced CAFs on OSCC progression.

Main Methods:

• In vitro: Assessed CAF marker α-smooth muscle actin (α-SMA) expression in TGF-β-treated NFs using qPCR and immunostaining. Analyzed OSCC cell migration via scratch assay.
• In vivo: Co-injected OSCC cells with TGF-β-treated or untreated NFs. Evaluated tumor growth, VEGF, MMP2, and MMP9 expression using qPCR and immunohistochemistry.

Main Results:

• In vitro, TGF-β significantly increased α-SMA expression in NFs and enhanced OSCC cell migration.
• In vivo, tumors co-injected with TGF-β-treated NFs showed increased growth and elevated expression of VEGF, MMP2, and MMP9.

Conclusions:

• TGF-β induces CAF differentiation, promoting OSCC progression through enhanced angiogenesis and extracellular matrix degradation.
• Targeting TGF-β presents a potential therapeutic avenue for OSCC.
• Novel strategies are needed to counteract pro-tumorigenic CAF effects in OSCC.