Satoru Sugie

Dysregulated HAI-2 Plays an Important Role in Renal Cell Carcinoma Bone Metastasis through Ligand-Dependent MET Phosphorylation

MET, a c-met proto-oncogene product and hepatocyte growth factor (HGF) receptor, is known to play an important role in cancer progression, including bone metastasis. In a previous study, we reported increased expression of MET and matriptase, a novel activator of HGF, in bone metastasis. In this study, we employed a mouse model of renal cell carcinoma (RCC) bone metastasis to clarify the significance of the HGF/MET signaling axis and the regulator of HGF activator inhibitor type-2 (HAI-2). Luciferase-transfected 786-O cells were injected into the left cardiac ventricle of mice to prepare the mouse model of bone metastasis. The formation of bone metastasis was confirmed by whole-body bioluminescent imaging, and specimens were extracted. Expression of HGF/MET-related molecules was analyzed. Based on the results, we produced HAI-2 stable knockdown 786-O cells, and analyzed invasiveness and motility. Expression of HGF and matriptase was increased in bone metastasis compared with the control, while that of HAI-2 was decreased. Furthermore, we confirmed increased phosphorylation of MET in bone metastasis. The expression of matriptase was upregulated, and both invasiveness and motility were increased significantly by knockdown of HAI-2. The significance of ligand-dependent MET activation in RCC bone metastasis is considered, and HAI-2 may be an important regulator in this system.

Pure Verrucous Carcinoma of the Penis: Two Cases

Verrucous carcinoma is a rare subtype of penile verruciform squamous cell carcinoma. However, in past literature, the diagnosis of verrucous carcinoma has been confused with giant condylomas, and papillary and warty carcinomas due to the absence of critical criteria in pathological diagnosis. We experienced two cases of penile verruciform tumor occurring in a 48-year-old Japanese male and an 88-year-old Japanese male. We performed partial penectomy without lymph node dissection after biopsy. Although we initially detected small palpablelymph node swelling in the latter case, unnecessary lymph node dissection could be avoided by pathological diagnosis using preoperative biopsy. The resected specimens were diagnosed in accordance with the World Health Organization (WHO) classification and current pathological reviews. Histopathological findings and immunohistochemical appearance were compatible with a diagnosis of verrucous carcinoma.