Hepatocyte Growth Factor and Macrophage-stimulating Protein "Hinge" Analogs to Treat Pancreatic Cancer
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
|---|---|
| Enthalten in: |
Current cancer drug targets - 19(2019), 10 vom: 27., Seite 782-795 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wright, John W [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 08.09.2020 Date Revised 08.09.2020 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.2174/1568009619666190326130008 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM295363517 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM295363517 | ||
| 003 | DE-627 | ||
| 005 | 20231225083510.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.2174/1568009619666190326130008 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0984.xml |
| 035 | |a (DE-627)NLM295363517 | ||
| 035 | |a (NLM)30914029 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wright, John W |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Hepatocyte Growth Factor and Macrophage-stimulating Protein "Hinge" Analogs to Treat Pancreatic Cancer |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 08.09.2020 | ||
| 500 | |a Date Revised 08.09.2020 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a Pancreatic cancer | |
| 650 | 4 | |a Ronreceptor | |
| 650 | 4 | |a angiotensin IV | |
| 650 | 4 | |a hepatocyte growth factor | |
| 650 | 4 | |a macrophage stimulating protein | |
| 650 | 4 | |a met receptor. | |
| 650 | 7 | |a HGF protein, human |2 NLM | |
| 650 | 7 | |a Oligopeptides |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins |2 NLM | |
| 650 | 7 | |a macrophage stimulating protein |2 NLM | |
| 650 | 7 | |a norleucyl-tyrosyl-leucyl-psi(CH2-NH2)(3-4)-histidyl-prolyl-phenylalanine |2 NLM | |
| 650 | 7 | |a Hepatocyte Growth Factor |2 NLM | |
| 650 | 7 | |a 67256-21-7 |2 NLM | |
| 700 | 1 | |a Church, Kevin J |e verfasserin |4 aut | |
| 700 | 1 | |a Harding, Joseph W |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Current cancer drug targets |d 2001 |g 19(2019), 10 vom: 27., Seite 782-795 |w (DE-627)NLM120490560 |x 1873-5576 |7 nnns |
| 773 | 1 | 8 | |g volume:19 |g year:2019 |g number:10 |g day:27 |g pages:782-795 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.2174/1568009619666190326130008 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 19 |j 2019 |e 10 |b 27 |h 782-795 | ||