Dysregulated growth and invasion characterize oral squamous cell carcinoma (SCC). SCC invasion into adjacent tissue requires integrin- mediated cell migration through the underlying extracellular matrix. Before they actively invade, the carcinoma cells must initiate nascent attachments to the underlying extracellular matrix and disengage their extensive junctional adhesions. In contrast to normal mucosal epithelium, where proliferation is restricted to basal keratinocytes, suprabasal oral SCC cells have lost their requirement for anchorage to extracellular matrix and continue to proliferate uncontrollably in the absence of basement membrane adhesions. The long-term goal of the proposed research is to define the importance of adhesion in regulating invasion, survival and growth in oral SCC cells. In this proposal three specific aims will be addressed: 1) Identify specific integrin-ligand pairs that induce uncoupling of intercellular adhesion and stimulate cell motility. 2) Determine whether disruption of oral SCC cell adhesion will modulate anchorage-independent survival and growth. The experiments will utilize human oral SCC cell lines and the animal provided in Core B with histopathology to be performed in Core C. Extensive interactions related to integrin adhesion and cell growth are planned with Project. The proposed studies will establish whether specific receptor families generate compensatory signals that regulate motility, survival and growth. This information will help expand our understanding, at the molecular, of the role of adhesion in controlling unregulated invasion and intratumoral proliferation of oral cancer.
| Haga, Takeshi; Uchide, Noboru; Tugizov, Sharof et al. (2008) Role of E-cadherin in the induction of apoptosis of HPV16-positive CaSki cervical cancer cells during multicellular tumor spheroid formation. Apoptosis 13:97-108 |
| Pickering, Victoria; Jay Gupta, R; Quang, Phuong et al. (2008) Effect of peripheral endothelin-1 concentration on carcinoma-induced pain in mice. Eur J Pain 12:293-300 |
| Dang, Dongmin; Atakilit, Amha; Ramos, Daniel M (2008) EMMPRIN modulates migration and deposition of TN-C in oral squamous carcinoma. Anticancer Res 28:2049-54 |
| Shiboski, Caroline H; Schmidt, Brian L; Jordan, Richard C K (2007) Racial disparity in stage at diagnosis and survival among adults with oral cancer in the US. Community Dent Oral Epidemiol 35:233-40 |
| Schmidt, Brian L; Pickering, Victoria; Liu, Stanley et al. (2007) Peripheral endothelin A receptor antagonism attenuates carcinoma-induced pain. Eur J Pain 11:406-14 |
| Pickering, Victoria; Jordan, Richard C K; Schmidt, Brian L (2007) Elevated salivary endothelin levels in oral cancer patients--a pilot study. Oral Oncol 43:37-41 |
| Dang, Dongmin; Bamburg, James R; Ramos, Daniel M (2006) Alphavbeta3 integrin and cofilin modulate K1735 melanoma cell invasion. Exp Cell Res 312:468-77 |
| Tugizov, Sharof; Berline, Jennifer; Herrera, Rossana et al. (2005) Inhibition of human papillomavirus type 16 E7 phosphorylation by the S100 MRP-8/14 protein complex. J Virol 79:1099-112 |
| Connelly, Stephen T; Macabeo-Ong, Maricris; Dekker, Nusi et al. (2005) Increased nitric oxide levels and iNOS over-expression in oral squamous cell carcinoma. Oral Oncol 41:261-7 |
| Kramer, Randall H; Shen, Xiaodong; Zhou, Hua (2005) Tumor cell invasion and survival in head and neck cancer. Cancer Metastasis Rev 24:35-45 |
Showing the most recent 10 out of 28 publications
