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Pegylated kunitz domain inhibitor suppresses hepsin-mediated invasive tumor growth and metastasis


, : Pegylated kunitz domain inhibitor suppresses hepsin-mediated invasive tumor growth and metastasis. Cancer Research 69(21): 8395-8402

The transmembrane serine protease hepsin is one of the most highly upregulated genes in prostate cancer. Here, we investigated its tumor-promoting activity by use of a mouse orthotopic prostate cancer model. First, we compared the tumor growth of low hepsin-expressing LnCaP-17 cells with hepsin-overexpressing LnCaP-34 cells. After implantation of cells into the left anterior prostate lobe, LnCaP-34 tumors not only grew faster based on increased serum prostate-specific antigen levels but also metastasized to local lymph nodes and, most remarkably, invaded the contralateral side of the prostate at a rate of 100% compared with only 18% for LnCaP-17 tumors. The increased tumor growth was not due to nonspecific gene expression changes and was not predicted from the unaltered in vitro growth and invasion of LnCaP-34 cells. A likely explanation is that the in vivo effects of hepsin were mediated by specific hepsin substrates present in the tumor stroma. In a second study, mice bearing LnCaP-34 tumors were treated with a PEGylated form of Kunitz domain-1, a potent hepsin active site inhibitor derived from hepatocyte growth factor activator inhibitor-1 (K(i)(app) 0.30 +/- 0.02 nmol/L). Treatment of established tumors with PEGylated Kunitz domain-1 decreased contralateral prostate invasion (46% weight reduction) and lymph node metastasis (50% inhibition). Moreover, serum prostate-specific antigen level remained reduced during the entire treatment period, reaching a maximal reduction of 76% after 5 weeks of dosing. The findings show that hepsin promotes invasive prostate tumor growth and metastasis and suggest that active site-directed hepsin inhibition could be effective in prostate cancer therapy.

US$19.90

PMID: 19843851

DOI: 10.1158/0008-5472.CAN-09-1995


Other references

Jonasson, G.; Billhult, A., 2014: Mandibular bone structure, bone mineral density, and clinical variables as fracture predictors: a 15-year follow-up of female patients in a dental clinic. To compare three mandibular trabeculation evaluation methods, clinical variables, and osteoporosis as fracture predictors in women. One hundred and thirty-six female dental patients (35-94A years) answered a questionnaire in 1996 and 201Using intr...

Bartole R., 1978: Structural lineaments of the Central Asian orogenic syntaxis from Landsat imageries; part 1. Atti Accademia Nazionale dei Lincei, Classe di Scienze Fisiche Matematiche e Naturali, Rendiconti, 1892-? 64(5): 485-489

Kiilavuori, K.; Sovijärvi, A.; Näveri, H.; Ikonen, T.; Leinonen, H., 1996: Effect of physical training on exercise capacity and gas exchange in patients with chronic heart failure. Decreased exercise capacity is the main factor restricting the daily life of patients with chronic congestive heart failure (CHF). We performed a controlled, randomized study to evaluate the effect of dynamic exercise training of moderate intensit...

Hobson, K.; Bright, D., 1994: A key to the Xyleborus of California, with faunal comments (Coleoptera: Scolyidae). Pan Pacific entomologist 70(4): 267-268

Rutledge F.N., 1976: Estrogen therapy a causal role in endometrial cancer. AJR (American Journal of Roentgenology) 127(6): 897-899

Davies, S.J.J.F., 1957: The gosling of the Magpie Goose. Emu, 57: 354-355

Lehtokangas, M., 1999: Feedforward neural network with adaptive reference pattern layer. A hybrid neural network architecture is investigated for modeling purposes. The proposed hybrid is based on the multilayer perceptron (MLP) network. In addition to the usual hidden layers, the first hidden layer is selected to be an adaptive refer...

Yanagisawa, K.; Masui, K.; Furutani, K.; Nomura, M.; Ura, M.; Yoshida, H., 2011: Does higher general trust serve as a psychosocial buffer against social pain? An NIRS study of social exclusion. Social exclusion evokes social pain in excluded individuals. Neuroimaging studies suggest that this social pain is associated with activation of the dorsal anterior cingulate cortex (dACC), with further regulation of social pain being reflected in...

Hamilton, B.; Richard, D., 2010: Crotalus oreganus lutosus great basin rattlesnake elevation. Herpetological Review 41(1): 90

Todd, Richard D., 2000: Genetics of attention deficit/hyperactivity disorder: Are we ready for molecular genetic studies?. Reports of possible genetic associations or linkages for attention deficit hyperactivity disorder are appearing at an increasing rate. As with many other neuropsychiatric disorders, claims of positive findings are frequently followed by negative r...