Overexpression of Transforming Growth Factor β1 in Head and Neck Epithelia Results in Inflammation, Angiogenesis, and Epithelial Hyperproliferation

Abstract

In the present study, we show that transforming growth factor ␤1 (TGF-␤1) was frequently overexpressed in human head and neck squamous cell carcinomas (HNSCCs) and adjacent tissues in comparison with normal head and neck tissues. To determine the role of TGF-␤1 overexpression in HNSCC carcinogenesis, we generated transgenic mice in which TGF-␤1 transgene expression can be induced in head and neck epithelia. TGF-␤1 transgene induction in head and neck epithelia, at levels similar to those in human HNSCCs, caused severe inflammation and angiogenesis. Consequently, TGF-␤1-transgenic epithelia exhibited hyperproliferation. These phenotypes correlated with enhanced Smad signaling in transgenic epithelia and stroma. Our study suggests that TGF-␤1 overexpression at early stages of HNSCC formation provides a tumor promoting microenvironment.

Smad3 Knockout Mice Exhibit a Resistance to Skin Chemical Carcinogenesis

“…The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was achieved by combining in vitro reverse transcription with quantitative polymerase chain reaction, which was performed in a Stratagene Mx3000P thermal cycler (Stratagene, La Jolla, CA; ref. 29). Briefly, 5 g of RNA from each sample were treated with DNase (Ambion, Austin, TX).…”

TGF-β and tumors—an ill-fated alliance

“…Although a heterogeneous disease, a major and common etiological risk factor is continuous exposure of head and neck epithelia to environmental carcinogens, with genetic and epigenetic alterations in oncogenes or tumor suppressor genes. TGF-β is reportedly overexpressed in pre-neoplastic lesions adjacent to HNSCC, relative to uninvolved mucosa [12], implicating TGF-β early during HNSCC development. In a mouse model, TGF-β1 transgene induction in head and neck epithelia caused severe inflammation and angiogenesis, evidence that TGF-β1 overexpression does provide a tempting tumor milieu [12].…”

“…TGF-β is reportedly overexpressed in pre-neoplastic lesions adjacent to HNSCC, relative to uninvolved mucosa [12], implicating TGF-β early during HNSCC development. In a mouse model, TGF-β1 transgene induction in head and neck epithelia caused severe inflammation and angiogenesis, evidence that TGF-β1 overexpression does provide a tempting tumor milieu [12]. As a model to dissect unequal relationships between host and tumor, we have examined immune cells and their products in the context of HNSCC.…”

Cadherin Expression and Progression of Squamous Cell Carcinomas of the Oral Cavity

“…Carcinoma cell adhesion on extracellular matrix proteins, including laminin , type I collagen and fibronectin (Lefort et al, 2011), induces N-cadherin expression. Another key regulator of N-cadherin is TGF-, which can act to carcinoma cells after the extracellular matrix degradation and promotes invasion of oral carcinomas (Imai et al, 1997;Lu et al, 2004).…”