Macrophage-Stimulating Protein

2012 ◽  
Keyword(s):  
Macrophage Stimulating Protein

Hepatocyte Growth Factor and Macrophage-stimulating Protein “Hinge” Analogs to Treat Pancreatic Cancer

2019 ◽  
Vol 19 (10) ◽  
pp. 782-795
Author(s):  
John W. Wright ◽  
Kevin J. Church ◽  
Joseph W. Harding
Keyword(s):  
Pancreatic Cancer ◽  
Signal Transduction ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Tumor Growth ◽  
Receptor Activation ◽  
Signal Transduction Pathways ◽  
Met Receptor ◽  
Macrophage Stimulating Protein ◽  
Hepatocyte Growth

Pancreatic cancer (PC) ranks twelfth in frequency of diagnosis but is the fourth leading cause of cancer related deaths with a 5 year survival rate of less than 7 percent. This poor prognosis occurs because the early stages of PC are often asymptomatic. Over-expression of several growth factors, most notably vascular endothelial growth factor (VEGF), has been implicated in PC resulting in dysfunctional signal transduction pathways and the facilitation of tumor growth, invasion and metastasis. Hepatocyte growth factor (HGF) acts via the Met receptor and has also received research attention with ongoing efforts to develop treatments to block the Met receptor and its signal transduction pathways. Macrophage-stimulating protein (MSP), and its receptor Ron, is also recognized as important in the etiology of PC but is less well studied. Although the angiotensin II (AngII)/AT1 receptor system is best known for mediating blood pressure and body water/electrolyte balance, it also facilitates tumor vascularization and growth by stimulating the expression of VEGF. A metabolite of AngII, angiotensin IV (AngIV) has sequence homology with the “hinge regions” of HGF and MSP, key structures in the growth factor dimerization processes necessary for Met and Ron receptor activation. We have developed AngIV-based analogs designed to block dimerization of HGF and MSP and thus receptor activation. Norleual has shown promise as tested utilizing PC cell cultures. Results indicate that cell migration, invasion, and pro-survival functions were suppressed by this analog and tumor growth was significantly inhibited in an orthotopic PC mouse model.

scholarly journals Molecular targets in cancer therapy: the Ron approach

2011 ◽  
pp. 215-224
Author(s):  
Serena Germano ◽  
Giovanni Gaudino
Keyword(s):  
Receptor Tyrosine Kinase ◽  
Molecular Targets ◽  
Clinical Intervention ◽  
Positive Association ◽  
Biological Indicators ◽  
Receptor Activation ◽  
Macrophage Stimulating Protein ◽  
Epithelial Cancers ◽  
Multiple Processes

The receptor tyrosine kinase Ron and its ligand, Macrophage Stimulating Protein (MSP), mediate multiple processes involved in the control of cell proliferation, migration and protection from apoptosis. Dysregulated signaling of Ron, due to hyperactivation or loss of negative regulation, is involved in tumor progression and metastasis. Growing evidence indicates that Ron is abnormally expressed and activated in certain types of primary epithelial cancers (i.e. breast, colon, lung, pancreas, bladder and thyroid), where it critically contributes to the maintenance of tumorigenic and invasive phenotype. Furthermore, a positive association between aberrant Ron expression and aggressive biological indicators as well as a worse clinical outcome have been reported in breast, bladder and thyroid carcinomas. Different approaches have proved effective in targeting receptor activation/expression both in vitro and in animal models, leading to reversion of the tumorigenic phenotype. Altogether these results show that Ron is an attractive molecular target for clinical intervention.

scholarly journals Protein phosphatase 1 binds to phospho-Ser-1394 of the macrophage-stimulating protein receptor

2003 ◽  
Vol 376 (3) ◽  
pp. 587-594 ◽  
Author(s):  
Massimo M. SANTORO ◽  
Giovanni GAUDINO ◽  
Emma VILLA-MORUZZI
Keyword(s):  
Protein Phosphatase ◽  
Growth Factor Receptor ◽  
Living Cells ◽  
Protein Phosphatase 1 ◽  
Serine Threonine Kinase ◽  
Macrophage Stimulating Protein ◽  
Protein Receptor ◽  
Ron Receptor ◽  
Different Origins

The tyrosine kinase Ron, receptor for MSP (macrophage-stimulating protein), displays several serine residues of unknown functions. Using [32P]H3PO4 metabolic labelling, we found that Ron is serine-phosphorylated and dephosphorylated in vitro by PP1 (protein phosphatase 1). PP1 associates with Ron obtained from cells of different origins. The association is stimulated by MSP or serum and is prevented by wortmannin, an inhibitor of the Akt/PKB (protein serine/threonine kinase B) pathway. Akt/PKB phosphorylates Ron Ser-1394, thus providing a docking site for 14-3-3 (scaffold proteins binding to phosphoserine/phosphothreonine-containing sequences). In living cells, PP1 binds to the Ron mutant S1394A, but the association is no longer regulated by serum, MSP or wortmannin. The role of PP1 association with Ron is highlighted by (1) Ser-1394 dephosphorylation by PP1 in vitro and in living cells, (2) loss of 14-3-3 association with Ron after Ser-1394 dephosphorylation by PP1 in vitro and (3) an increase in 14-3-3 association after PP1 inactivation in living cells. These results suggest that PP1 can modulate the downstream Ron signalling generated by MSP via Akt/PKB and 14-3-3 binding. This is the first report on ligand-regulated association of PP1 with a growth factor receptor.

scholarly journals Analogs of the hepatocyte growth factor and macrophage-stimulating protein hinge regions act as Met and Ron dual inhibitors in pancreatic cancer cells

2016 ◽  
Vol 27 (8) ◽  
pp. 766-779 ◽  
Author(s):  
Kevin J. Church ◽  
Brett R. Vanderwerff ◽  
Rachelle R. Riggers ◽  
Michelle D. McMicheal ◽  
Beatriz Mateo-Victoriano ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cancer Cells ◽  
Macrophage Stimulating Protein ◽  
Pancreatic Cancer Cells ◽  
Dual Inhibitors ◽  
Hepatocyte Growth

scholarly journals The macrophage stimulating protein/RON system: a potential novel target for prevention and treatment of endometriosis

2005 ◽  
Vol 11 (5) ◽  
pp. 345-349 ◽  
Author(s):  
S. Matsuzaki ◽  
M. Canis ◽  
J.L. Pouly ◽  
P. Dechelotte ◽  
K. Okamura ◽  
...  
Keyword(s):  
Macrophage Stimulating Protein ◽  
System A ◽  
Prevention And Treatment ◽  
Novel Target

Molecular Cloning of Rat Macrophage-Stimulating Protein and Its Involvement in the Male Reproductive System

1996 ◽  
Vol 227 (1) ◽  
pp. 273-280 ◽  
Author(s):  
Kazuiku Ohshiro ◽  
Atsushi Iwama ◽  
Kenjiro Matsuno ◽  
Taichi Ezaki ◽  
Osamu Sakamoto ◽  
...  
Keyword(s):  
Molecular Cloning ◽  
Reproductive System ◽  
Male Reproductive System ◽  
Macrophage Stimulating Protein
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