title: Loss of the α2β1 integrin alters human papilloma virus-induced squamous carcinoma progression in vivo and in vitro.
abstract: Expression of the α2β1 integrin, a receptor for collagens and laminin, is altered during tumor progression. Recent studies have linked polymorphisms in the α2 integrin gene with oral, squamous cell carcinoma (SCC). To determine the α2β1 integrin's role in SCC progression, we crossed α2-null mice with K14-HPV16 transgenic animals. Pathological progression to invasive carcinoma was evaluated in HPV-positive, α2-null (HPV/KO) and HPV-positive, wild-type (HPV/WT) animals. α2β1 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 α2β1 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 α2β1 integrin expression by HPV-transformed keratinocytes modulates SCC growth and progression.
authors: Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors: Thuy
authors: T
authors: Tran
authors: Brittney
authors: B
authors: Barlow
authors: Lynda
authors: L
authors: O'Rear
authors: Brenda
authors: B
authors: Jarvis
authors: Zhengzhi
authors: Z
authors: Li
authors: Kent
authors: K
authors: Dickeson
authors: William
authors: W
authors: Dupont
authors: Mary
authors: M
authors: Zutter
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology* / Q000821:virology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D018450:Disease Progression; D052162:Human papillomavirus 16 / Q000472:pathogenicity*; D006801:Humans; D038982:Integrin alpha2beta1 / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D009368:Neoplasm Transplantation; D030361:Papillomavirus Infections
chemical_list: D038982:Integrin alpha2beta1