geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Antibodies neutralizing hepsin protease activity do not impact cell growth but inhibit invasion of prostate and ovarian tumor cells in culture


, : Antibodies neutralizing hepsin protease activity do not impact cell growth but inhibit invasion of prostate and ovarian tumor cells in culture. Cancer Research 66(7): 3611-3619

Hepsin is a type II transmembrane serine protease that is expressed in normal liver, and at lower levels in kidney, pancreas, and testis. Several studies have shown that hepsin mRNA is significantly elevated in most prostate tumors, as well as a significant fraction of ovarian and renal cell carcinomas and hepatomas. Although the overexpression of mRNA in these tumors has been extensively documented, there has been conflicting literature on whether hepsin plays a role in tumor cell growth and progression. Early literature implied a role for hepsin in human tumor cell proliferation, whereas recent studies with a transgenic mouse model for prostate cancer support a role for hepsin in tumor progression and metastases. To evaluate this issue further, we have expressed an activatable form of hepsin, and have generated a set of monoclonal antibodies that neutralize enzyme activity. The neutralizing antibodies inhibit hepsin enzymatic activity in biochemical and cell-based assays. Selected neutralizing and nonneutralizing antibodies were used in cell-based assays with tumor cells to evaluate the effect of antibodies on tumor cell growth and invasion. Neutralizing antibodies failed to inhibit the growth of prostate, ovarian, and hepatoma cell lines in culture. However, potent inhibitory effects of the antibodies were seen on invasion of ovarian and prostate cells in transwell-based invasion assays. These results support a role for hepsin in tumor cell progression but not in primary tumor growth. Consistent with this, immunohistochemical experiments with a mouse monoclonal antibody reveal progressively increased staining of prostate tumors with advanced disease, and in particular, extensive staining of bone metastatic lesions.

US$19.90

PMID: 16585186

DOI: 10.1158/0008-5472.CAN-05-2983


Other references

Kovacs, J., 1971: Cooperation in viticulture in the wine producing areas of Eger and Matraalja. Sarkany Pal Az Elelmiszergazdasag Vertikalis Koop: 49-176

Lannes, M.; Teitelbaum, J.; del Pilar Cortés, M.; Cardoso, M.; Angle, M., 2012: Milrinone and homeostasis to treat cerebral vasospasm associated with subarachnoid hemorrhage: the Montreal Neurological Hospital protocol. For the treatment of cerebral vasospasm, current therapies have focused on increasing blood flow through blood pressure augmentation, hypervolemia, the use of intra-arterial vasodilators, and angioplasty of proximal cerebral vessels. Through a lar...

Wei, Z-sheng.; Hong, M-fan.; Su, Q-xi.; Wang, X-hui.; Yu, Q-yun.; Peng, Z-xing.; Zhang, M-xing.; Jie, A.; Wang, R.; Huang, Y-qing., 2011: Super-high-dose methylprednisolone does not improve efficacy or induce glucocorticoid resistance in experimental allergic encephalomyelitis. To investigate whether a super-high dose (SHD) of methylprednisolone (MP) improves its efficacy or induces glucocorticoid (GC) resistance, and to explore the potential mechanisms of GC resistance in experimental allergic encephalomyelitis (EAE). T...

Scherler, Pierre., 1995: Les Coleopteres de la Grande Caricaie (rive sud-est du lac de Neuchatel). Bulletin Romand d'Entomologie. Avril; 131: 31-54

Choi, Y.M.; Robbie, G.; Chiou, W.L., 1994: First-pass accumulation of drugs in rat gut tissue studied by steady-state perfusion and closed-loop absorption methods. Pharmaceutical Research (New York) 11(10 SUPPL ): S351

Guzman, R.; Looby, J.F.; Schendel, S.A.; Edwards, M.S.B., 2011: Fronto-orbital advancement using an en bloc frontal bone craniectomy. Fronto-orbital advancement is a procedure commonly performed in craniofacial centers for coronal and metopic suture synostosis. Several variations of the technique have been reported. To describe our modifications to the anterior cranioplasty proc...

Ruzicka, L., 1953: The isoprene rule and the biogenesis of terpenic compounds. Experientia 9(10): 357-367

Powell A.A.; Matthews S., 1984: Evidence for repair processes in hydrated seeds and their role in seed invigoration. Hortscience 19(3 SECT 2): 568

Málek, P.; Kolc, J.; Hasková, V.; Zástava, V., 1969: Antilymphocyte serum and lymphatic system. I. The effect of regional administration on the survival of skin allografts. Transplantation 8(4): 333-337

Stearn C.W., 1992: Petridiostroma new name for petrostroma stearn 1991 not petrostroma doderlein 1892. Journal of Paleontology 66(3): 531