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Modification of Tumor Cell Growth

Wen-chang Lin, PhD; Satoshi Yasumura, MD, PhD; Theresa L. Whiteside, PhD

Arch Otolaryngol Head Neck Surg. 1993;119(11):1229-1235.

Abstract
Objective
Human squamous cell carcinomas of the head and neck (SCCHN) have been shown to express interleukin 2 receptor (IL-2R), and binding of the ligand, IL-2, to the receptor results in tumor growth inhibition in vitro or in vivo in an SCCHN xenograft model in nude mice. To optimize growth inhibitory effects of IL-2, expression of the or chains of IL-2R in SCCHN was experimentally modified by transfection of tumor cells with the respective IL-2R genes or the lacZ gene as control.

Design
Using plasmid vectors containing the IL-2R chain gene under the control of a cytomegalovirus promoter or the IL-2R chain gene under the control of a Rous sarcoma virus promoter, the IL-2R genes were transferred by lipofection into SCCHN cell lines. Stable transfectants were selected, cloned by limiting dilution, and clones were compared with the parental cell lines for their sensitivity to the growth-inhibitory effect of IL-2.

Results
Transfer of the IL-2R chain gene into SCCHN cells resulted in significant upregulation of expression of the IL-2R chain on tumor cell surface but not in increased tumor growth inhibition by IL-2. In contrast, SCCHN IL-2R transfectants, which expressed IL-2R chain transcripts as confirmed in RNase protection assays, were significantly inhibited in growth and were sensitive to lower concentrations of IL-2 than the parental cell lines.

Conclusions
Genetic modification of IL-2R expression on IL-2R—positive tumor cells in culture significantly alters their proliferative response to IL-2. These observations open a way for developing new strategies for therapy of SCCHN based on direct interactions of IL-2 with its receptor on tumor cells.

(Arch Otolaryngol Head Neck Surg. 1993;119:1229-1235)

Author Affiliations
From the Department of Pathology, University of Pittsburgh (Pa) School of Medicine, and Immunologic Monitoring and Diagnostic Laboratory, Pittsburgh Cancer Institute.

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