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Dermatology - Oncology

Loss of the a2ß1 Integrin Alters Human Papilloma Virus-Induced Squamous Carcinoma Progression In Vivo and In Vitro
Published: Thursday, October 27, 2011
Author: Thuy Tran et al.

by Thuy Tran, Brittney Barlow, Lynda O'Rear, Brenda Jarvis, Zhengzhi Li, Kent Dickeson, William Dupont, Mary Zutter

Expression of the a2ß1 integrin, a receptor for collagens and laminin, is altered during tumor progression. Recent studies have linked polymorphisms in the a2 integrin gene with oral, squamous cell carcinoma (SCC). To determine the a2ß1 integrin's role in SCC progression, we crossed a2-null mice with K14-HPV16 transgenic animals. Pathological progression to invasive carcinoma was evaluated in HPV-positive, a2-null (HPV/KO) and HPV-positive, wild-type (HPV/WT) animals. a2ß1 integrin expression stimulated progression from hyperplasia and papillomatosis to dysplasia with concomitant dermal mast cell infiltration. Moreover, lymph node metastasis was decreased by 31.3% in HPV/KO, compared to HPV/WT, animals. To evaluate the integrin-specific impact on the malignant epithelium versus the microenvironment, we developed primary tumor cell lines. Although transition from dysplasia to carcinoma was unaltered during spontaneous tumor development, isolated primary HPV/KO SCC cell lines demonstrated decreased migration and invasion, compared to HPV/WT cells. When HPV/WT and HPV/KO SCC cells were orthotopically injected into WT or KO hosts, tumor a2ß1 integrin expression resulted in decreased tumor latency, regardless of host integrin status. HPV/WT SCC lines failed to demonstrate a proliferative advantage in vitro, however, the HPV/WT tumors demonstrated increased growth compared to HPV/KO SCC lines in vivo. Although contributions of the integrin to the microenvironment cannot be excluded, our studies indicate that a2ß1 integrin expression by HPV-transformed keratinocytes modulates SCC growth and progression.