PARENT SESSION
1:30 PM to 3:30 PM
Wednesday, April 25, 2001
Poster Session 28 Tumor Physiology and Microenvironments
Room: Exhibition Center

(P28-372) Impact of egf-receptor blockade on squamous cell carcinoma radiation response in the niks normal tissue microenvironment tumor model.

Pickart, Michael^1,2, Bachman, Timothy¹, Allen-Hoffmann, Lynn^1,2, Harari, Paul^1,2, ^{1 2}

ABSTRACT-
Recent findings suggest that radiation-induced activation of the epidermal growth factor receptor (EGFR) and downstream mitogen-activated protein kinase pathway may influence survival and repopulation of squamous cell carcinoma (SCC) cells growing in monolayer culture. C225, a monoclonal antibody directed against the EGFR, has been shown to block EGFR activation and SCC cell growth in monolayer cell culture and animal models. In the current work, we have used our recently developed normal tissue microenvironment (NTM) model of tumor growth to examine the effect of C225 on both the growth and survival of SCC13y and human keratinocytes (NIKS cells) following irradiation. Toward this end, we have established methods of fluorescent image analysis, confocal microscopy, and 3D-modeling to map and quantitate the growth of green fluorescent protein (GFP) expressing SCC13y cells (SCC13y^GFP) growing in the context of a NIKS-based fully stratified epithelium. The potential of C225 to modulate radiation-induced apoptosis and EGFR signaling in monolayer culture and the NIKS NTM model is compared. Preliminary data suggest that NTM cultures are more resistant to radiation than monolayer cell cultures. Radiation and C225 can disrupt the epithelial tissue architecture surrounding foci of SCC13y^GFP cell growth, but do not appear to alter the capacity of the tissue to heal. We hypothesize that the cell-cell interactions present in a self-renewing tissue, e.g. skin, may account for response differences between the NIKS NTM tumor model and monolayer cell culture to radiation and C225. Our goal is to investigate cellular and molecular responses to radiation and chemotherapeutic agents in an in vitro human tissue model. Supported in part by grants from the Robert Draper Technology Innovation Fund (LAH), UWCCC Pilot Project Grant (LAH & PMH), and NIH grants AR40284, AR42853 (LAH). C225 was provided by ImClone Systems, New York (PMH).

KEYWORDS: egfr, green fluorescence protein (gfp), organotypic culture, squamous cell carcinoma (scc)