Enhancement of head and neck squamous cell carcinoma proliferation, invasion, and metastasis by tumor-associated fibroblasts in preclinical models

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) has had little improvement in mortality rates in decades. A clearer understanding of the HNSCC tumor microenvironment will aid in finding more effective targeted therapies for this disease. Tumor-associated fibroblasts (TAFs) are the largest stromal cellular components of the tumor microenvironment in HNSCC.

Methods: We isolated TAFs from clinical HNSCC cases and propagated in vitro. The effects of TAF-secreted paracrine factors on in vitro HNSCC migration, invasion, and proliferation was assessed. The effect of TAFs on HNSCC growth and metastases was determined in an orthotopic floor-of-the-mouth tumor model.

Results: TAF-conditioned media increased HNSCC cell migration, invasion, and proliferation. TAFs increased HNSCC tumor growth and metastases in vivo.

Conclusion: TAFs play a major role in increasing tumor growth and metastasis in HNSCC. Targeting the tumor stroma may be important to reduce the rate of HNSCC metastasis.

Keywords: head and neck cancer; invasion; metastasis; tumor microenvironment; tumor-associated fibroblasts.