**Role of Tumor Microenvironment in Head and Neck Squamous Cell Carcinoma**

160 Squamous Cell Carcinoma

[30] Murakami A, Nakagawa T, Kaneko M, Nawata S, Takeda O, Kato H, Sugino N:

[32] Murakami A, Nakagawa T, Fukushima C, Torii M, Sueoka K, Nawata S, Takeda O,

[33] Nakagawa T, Murakami A, Torii M, Nawata S, Takeda O, and Sugino N: E-cadherin

the decrease in E-cadherin expression. Int J Oncol 29: 1231-1235, 2006 [31] Hirakawa H, Nawata S, Sueoka K, Murakami A, Takeda O, Numa F, Kato H, and

antigen. Exp Cell Res 299: 525-532, 2004

lymph node metastasis. Oncol Rep 19: 99-104, 2008

Oncol Rep 11: 415-419, 2004

Oncol Rep 18: 175-179, 2007

cancer cells by activating serine proteinase inhibitor squamous cell carcinoma

Suppression of SCC antigen promotes cancer cell invasion and migration through

Sugino N: Regulation of squamous cell carcinoma antigen production by Ecadherin mediated cell-cell adhesion, ion in squamous cell carcinoma cell line.

Ishikawa H, Sugino N: Relationship between decreased expression of squamous cell carcinoma antigen 2 and E-cadherin in primary cervical cancer lesions and

increases squamous cell carcinoma antigen expression through phosphatidylinositol-3 kinase-Akt pathway in squamous cell carcinoma cell lines.

**10** 

*USA* 

**The Cellular Microenvironment of Head** 

Head and neck squamous cell carcinoma (HNSCC) tumors function much like organs with support from multiple cell lineages. Tobacco and alcohol abuse are strongly correlated with the disease. Environmental carcinogen exposure introduces genetic alterations not only in the epithelial cells but also in the surrounding stroma contributing to tumor initiation and progression [1]. Factors and cells that do not support tumor growth are commonly downregulated or mitigated in the tumor microenvironment. Several classes of stromal cells that exist in close proximity with HNSCC tumors have been identified. These include fibroblasts, immune cells and cells involved in vascular growth. Each of these cell types are involved in molecular cross-talk with the tumor resulting in tumor progression (Figure 1). Here we highlight each of the major cell types present in the HNSCC tumor microenvironment. Well characterized molecular markers have been used to identify the specific stromal cellular components (Table 1). There continues to be a tremendous need for improved understanding of the role of each of these cell types in tumor growth, dissemination and resistance to therapies. Tumor-associated stroma can support tumor cell proliferation, angiogenesis and invasion making them potential therapeutic targets. Since de novo acquisition of genetic mutations is not common in stromal cells they may be less prone to developing resistance to therapy via genomic instability. The synergistic relationship between stroma and tumor cells suggests that stroma targeted intervention may have a synergistic role in primary cancer therapy. However, fibrosis that follows surgery, chemotherapy and radiotherapy may trigger the release of stromal factors that support recurrence and metastasis. Thus stroma targeted therapies may emerge as important in

Fibroblasts are important components of the mesenchymal stroma Though they appear morphologically similar, fibroblasts show large differences in their functions and patterns of gene expression depending on their anatomical site of origin. Under normal physiological conditions, fibroblasts help maintain the boundary between the epithelial cells and the

**1. Introduction** 

adjuvant setting.

Corresponding Author

 \*

**2. Tumor associated fibroblasts** 

**and Neck Squamous Cell Carcinoma** 

*Department of Otolaryngology, University of Pittsburgh and* 

*University of Pittsburgh Cancer Institute, Pittsburgh* 

Maya Mathew and Sufi Mary Thomas\*
