Figure 5

HIF-1α expression in tumor epithelium is required for metastasis. (A) Mean number of micrometastases ± SEM observed when lungs were harvested at the same time as the primary tumors (> 1,000 mm³) (n = 9 wild-type (WT) and 14 knockout (KO) recipients, *P < 0.05, unpaired Student's t-test). (B) Enhancement of lung metastases when WT and KO primary tumors were surgically resected at equivalent volumes (500 to 750 mm³), followed by 8 weeks of survival (n = 32 WT and 22 KO recipients, *P < 0.05, Student's t-test). (C) Representative images of lungs harvested from WT or KO mammary tumor epithelial cell recipients 8 weeks after tumor resection (original magnification, ×50). (D) The impact of HIF-1α expression in tumor cells on the survival of recipients following tumor resection. A subset of animals subjected to primary tumor resection was allowed to survive until moribund due to metastasis. The morbidity hazard ratio was 3.78 times higher when hosts bore WT tumors (n = 14 WT and 15 KO hosts, logrank test, P = 0.00039, 95% CI = 1.53 to 9.31).