Figure 1. Loss of TSP-1 leads to decreased survival and rapid progression of Kras^G12D-mediated lung tumorigenesis.

(A) Overall Kras^G12D×Tsp-1^+/+ and Kras^G12D×Tsp-1^–/– mouse survival after induction of Kras^G12D expression via intranasal instillation of Ad-Cre. Data represent mean ± SEM. P = 0.0064. (B) H&E images of lungs at the indicated times after oncogenic Kras activation. Lungs were harvested, stained with H&E, and scored for tumor pathology. (C) TSP-1 expression in oncogenic Kras^G12D-driven lung lesions at the indicated times after Ad-Cre infection. Isolated Kras^G12D×Tsp-1^+/+ lungs were examined for TSP-1 expression by immunofluorescence. Kras^G12D×Tsp-1^–/– lung tumors were immunostained for TSP-1 as a negative control. Corresponding H&E images of tumors are shown below. AAH, atypical adenomatous hyperplasia. (D) Time course analysis of TSP-1 expression upon oncogenic Kras activation in primary murine adult lung fibroblasts. Kras^G12D×Tsp-1^+/+ lung fibroblasts were infected with Ad-Cre, harvested at the indicated time points, and analyzed for TSP-1 expression by immunoblotting. Kras^G12D×Tsp-1^–/– fibroblasts served as a negative control. (E) Representative images of TSP-1 expression by immunofluorescence in normal human lungs and lung adenocarcinomas at different stages. Scale bars: 1 mm (B, ×40); 50 μm (B, ×400; C; and E).