Regulation of the Angiogenesis of Acquired Middle Ear Cholesteatomas by Inhibitor of DNA Binding Transcription Factor Id1 Angiogenesis in Middle Ear Cholesteatomas

Fukudome S, Wang C, Hamajima Y, et al. — Fri, 01 Mar 2013 00:00:00 GMT

Importance

The aggressive growth of cholesteatoma in the middle ear involves the angiogenesis of the cholesteatomal perimatrix. However, which transcription factor is involved in this process remains unclear.

Objective

To identify a transcription factor that supports the aggressive growth of cholesteatoma by controlling the angiogenesis of cholesteatoma in the middle ear milieu.

Design

We used clinical specimens for the profiling of angiogenic factors and their regulatory transcription factors in cholesteatoma. Human skin keratinocytes and endothelial cells were used for evaluation of the effects of candidate transcription factor on the angiogenic factor regulation and endothelial cell proliferation.

Setting

University departments of otolaryngology–head and neck surgery.

Participants

Eight clinical cholesteatomal and 8 control specimens were used for cellular and molecular biologic evaluation. An additional 8 cholesteatomal and 8 aural skin specimens were used for microarray studies.

Main Outcome Measures

The expression of vascular endothelial growth factor, interleukin 8, and cyclooxygenase 2 as measured by means of immunohistochemistry and molecular biologic methods.

Results

Human aural cholesteatomal specimens were rich in the expression of angiogenic factors such as vascular endothelial growth factor in the cholesteatomal matrix and perimatrix, accompanied by the transcription factor inhibitor of DNA binding (Id1). We found Id1 to be an essential regulator of vascular endothelial growth factor. In addition, potent angiogenic factors, including interleukin 8 and cyclooxygenase 2, were regulated by Id1 via different molecular mechanisms.

Conclusions and Relevance

The transcription factor Id1 controls the angiogenesis of cholesteatoma through the regulation of vascular endothelial growth factor, interleukin 8, and cyclooxygenase 2, which are responsible for the angiogenesis of cholesteatoma. Id1 may serve as a good target for the treatment of cholesteatomal progression in the middle ear milieu.

JAMA Otolaryngology–Head & Neck Surgery: Middle/External Ear Disorders Topic Collection

Regulation of the Angiogenesis of Acquired Middle Ear Cholesteatomas by Inhibitor of DNA Binding Transcription Factor Id1 Angiogenesis in Middle Ear Cholesteatomas