Clinical Cancer Research, Vol 4, Issue 10 2521-2528, Copyright © 1998 by American Association for Cancer Research

ARTICLES

Bystander effect in the adenovirus-mediated wild-type p53 gene therapy model of human squamous cell carcinoma of the head and neck

DK Frank, MJ Frederick, TJ Liu and GL Clayman
Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.

In models of human lung and head and neck cancer, there have been anecdotal reports of a bystander effect in wild-type p53 gene therapy, an apoptosis-inducing molecular intervention strategy. These reports do not definitively demonstrate the presence of a bystander effect, nor do they elucidate requirements for or characteristics of this phenomenon. We have investigated human squamous cell carcinoma of the head and neck for the presence and requirements of a bystander effect after wild-type p53 gene transduction. Recombinant adenovirus, Ad-p53, was used for wild-type p53 gene transfers. To investigate the role of intercellular contact between p53-transduced and nontransduced cells in mediating a growth inhibitory (bystander) effect on nontransduced cells, coculturing experiments were conducted on human squamous cell carcinoma of the head and neck cell lines TU138 and TU167. For TU138, 29% growth inhibition of nontransduced cells was demonstrated 3 days after p53-transduced and nontransduced cells were cocultured with intercellular contact. This growth inhibition was abolished when cells were cocultured without intercellular contact. TU167 did not demonstrate a bystander effect under any coculturing condition. Supernatant from Ad-p53-infected TU138 and TU167 cells demonstrated no growth-inhibitory effect on respective nontransduced cells. The bystander effect in the adenovirus-mediated wild-type p53 gene therapy model of squamous cell carcinoma of the head and neck, when present, requires intercellular contact. Possible mechanisms of the observed in vitro bystander effect are discussed.

This article has been cited by other articles:

				M. S. Teng, M. S. Brandwein-Gensler, M. S. Teixeira, J. A. Martignetti, and D. C. Duffey A Study of TRAIL Receptors in Squamous Cell Carcinoma of the Head and Neck Arch Otolaryngol Head Neck Surg, May 1, 2005; 131(5): 407 - 412. [Abstract] [Full Text] [PDF]

				C. Moon, Y. Oh, and J. A. Roth Current Status of Gene Therapy for Lung Cancer and Head and Neck Cancer Clin. Cancer Res., November 1, 2003; 9(14): 5055 - 5067. [Abstract] [Full Text] [PDF]

				A. Hasenburg, D.-C. Fischer, X.-W. Tong, A. Rojas-Martinez, R. H. Kaufman, I. Ramzy, P. Kohlberger, M. Orlowska-Volk, E. Aguilar-Cordova, and D. G. Kieback Adenovirus-Mediated Thymidine Kinase Gene Therapy for Recurrent Ovarian Cancer: Expression of Coxsackie-Adenovirus Receptor and Integrins {alpha}v{beta}3 and {alpha}v{beta}5 Reproductive Sciences, May 1, 2002; 9(3): 174 - 180. [Abstract] [PDF]

				J. L. Carroll, L. L. Nielsen, S. B. Pruett, and J. M. Mathis The Role of Natural Killer Cells in Adenovirus-mediated p53 Gene Therapy Mol. Cancer Ther., November 1, 2001; 1(1): 49 - 60. [Abstract] [Full Text] [PDF]

				K. REZNIKOV, L. KOLESNIKOVA, A. PRAMANIK, K. TAN-NO, I. GILEVA, T. YAKOVLEVA, R. RIGLER, L. TERENIUS, and G. BAKALKIN Clustering of apoptotic cells via bystander killing by peroxides FASEB J, September 1, 2000; 14(12): 1754 - 1764. [Abstract] [Full Text]

				G. Niu, R. Heller, R. Catlett-Falcone, D. Coppola, M. Jaroszeski, W. Dalton, R. Jove, and H. Yu Gene Therapy with Dominant-negative Stat3 Suppresses Growth of the Murine Melanoma B16 Tumor in Vivo Cancer Res., October 1, 1999; 59(20): 5059 - 5063. [Abstract] [Full Text] [PDF]

				P.-X. Li, J. Wong, A. Ayed, D. Ngo, A. M. Brade, C. Arrowsmith, R. C. Austin, and H. J. Klamut Placental Transforming Growth Factor-beta Is a Downstream Mediator of the Growth Arrest and Apoptotic Response of Tumor Cells to DNA Damage and p53 Overexpression J. Biol. Chem., June 23, 2000; 275(26): 20127 - 20135. [Abstract] [Full Text] [PDF]