Tumors formed by heparanase-transfected cells metastasize to bone and enhance osteoclastogenesis. (A) Immunostaining for human kappa light chain (brown) detects CAG tumor cells present in the femur of an animal injected subcutaneously with heparanase-transfected cells. (Inset) Cells stained for kappa light chain are not detected in the femur taken from a mouse injected subcutaneously with the control-transfected CAG cells. (B) Extensive osteoclast activity is detected by TRAP staining (red) in femurs where heparanase-transfected CAG cells have metastasized. (Inset) Little osteoclast activity is detected in control animals that lack bone metastases. (Original magnification, × 200.)