c-Met tyrosine kinase receptor expression and function in human and canine osteosarcoma cells

E. Gregory MacEwen; Jon Kutzke; Jennifer Carew; Josep Pastor; Julie A. Schmidt; Rachel Tsan; Douglas H. Thamm; Robert Radinsky

doi:10.1023/A:1025404603315

c-Met tyrosine kinase receptor expression and function in human and canine osteosarcoma cells

E. Gregory MacEwen, Jon Kutzke, Jennifer Carew, Josep Pastor, Julie A. Schmidt, Rachel Tsan, Douglas H. Thamm, Robert Radinsky

Research output: Contribution to journal › Article › peer-review

53 Scopus citations

Abstract

To further characterize the role of hepatocyte growth factor-scatter factor (HGF-SF) and its receptor (c-Met) in osteosarcoma (OS), human OS cell lines with low (SAOS-2) and high (SAOS-LM2) metastatic potential, and cell lines derived from spontaneous canine OS were studied. All cell lines were evaluated for c-Met and HGF-SF expression and receptor activation using Northern, RT-PCR, and Western blot analyses, respectively. Functional activity of receptor-ligand interaction was measured using c-Met phosphorylation status, proliferation assays (anchorage-dependent and -independent), Matrigel invasion, modulation of urokinase plasminogen activator (uPA) expression, and cell dispersion (scattering). All cell lines exhibited steady-state mRNA expression of c-Met. The canine OS cell lines also expressed HGF-SF mRNA as determined by RT-PCR analysis. Western analysis showed c-Met protein expression and HGF-stimulated (human) or constitutive (canine) receptor autophosphorylation. Treatment with recombinant human HGF resulted in enhanced proliferation in 3 of 5 OS cell lines and enhanced colony formation in 2 of 5 OS cell lines. Matrigel invasion was significantly enhanced in 3 of the cell lines and uPA levels were significantly increased in the SAOS-2 cells following HGF treatment. Scattering was enhanced in both the SAOS-2 and SAOS-LM2 cells. These data support the involvement of c-Met and HGF-SF in the growth and progression of human and canine OS, and may offer new targets for the development of therapeutic strategies for OS.

Original language	English (US)
Pages (from-to)	421-430
Number of pages	10
Journal	Clinical and Experimental Metastasis
Volume	20
Issue number	5
DOIs	https://doi.org/10.1023/A:1025404603315
State	Published - 2003
Externally published	Yes

Keywords

Canine
Hepatocyte growth factor
Human
Invasion
Molecular determinants
Osteosarcoma
Scatter factor
Urokinase plasminogen activator
c-Met

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1023/A:1025404603315

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@article{6058db26c73d449ebcb5317b9b902be0,

title = "c-Met tyrosine kinase receptor expression and function in human and canine osteosarcoma cells",

abstract = "To further characterize the role of hepatocyte growth factor-scatter factor (HGF-SF) and its receptor (c-Met) in osteosarcoma (OS), human OS cell lines with low (SAOS-2) and high (SAOS-LM2) metastatic potential, and cell lines derived from spontaneous canine OS were studied. All cell lines were evaluated for c-Met and HGF-SF expression and receptor activation using Northern, RT-PCR, and Western blot analyses, respectively. Functional activity of receptor-ligand interaction was measured using c-Met phosphorylation status, proliferation assays (anchorage-dependent and -independent), Matrigel invasion, modulation of urokinase plasminogen activator (uPA) expression, and cell dispersion (scattering). All cell lines exhibited steady-state mRNA expression of c-Met. The canine OS cell lines also expressed HGF-SF mRNA as determined by RT-PCR analysis. Western analysis showed c-Met protein expression and HGF-stimulated (human) or constitutive (canine) receptor autophosphorylation. Treatment with recombinant human HGF resulted in enhanced proliferation in 3 of 5 OS cell lines and enhanced colony formation in 2 of 5 OS cell lines. Matrigel invasion was significantly enhanced in 3 of the cell lines and uPA levels were significantly increased in the SAOS-2 cells following HGF treatment. Scattering was enhanced in both the SAOS-2 and SAOS-LM2 cells. These data support the involvement of c-Met and HGF-SF in the growth and progression of human and canine OS, and may offer new targets for the development of therapeutic strategies for OS.",

keywords = "Canine, Hepatocyte growth factor, Human, Invasion, Molecular determinants, Osteosarcoma, Scatter factor, Urokinase plasminogen activator, c-Met",

author = "MacEwen, {E. Gregory} and Jon Kutzke and Jennifer Carew and Josep Pastor and Schmidt, {Julie A.} and Rachel Tsan and Thamm, {Douglas H.} and Robert Radinsky",

note = "Funding Information: The authors wish to dedicate this manuscript to their esteemed colleague and co-author, the late Dr E. Gregory MacEwen. This work was supported in part by grants from the NIH National Cancer Institute CA RO1 64648 (MacEwen), and CA R29 67952 (Radinsky), and a Supplemental Consortium Grant from NIH (Radinsky). The authors thank Richard Grygiel and Erica Wick for their assistance in performing the in vitro procedures.",

year = "2003",

doi = "10.1023/A:1025404603315",

language = "English (US)",

volume = "20",

pages = "421--430",

journal = "Clinical and Experimental Metastasis",

issn = "0262-0898",

publisher = "Springer Science and Business Media B.V.",

number = "5",

}

TY - JOUR

T1 - c-Met tyrosine kinase receptor expression and function in human and canine osteosarcoma cells

AU - MacEwen, E. Gregory

AU - Kutzke, Jon

AU - Carew, Jennifer

AU - Pastor, Josep

AU - Schmidt, Julie A.

AU - Tsan, Rachel

AU - Thamm, Douglas H.

AU - Radinsky, Robert

N1 - Funding Information: The authors wish to dedicate this manuscript to their esteemed colleague and co-author, the late Dr E. Gregory MacEwen. This work was supported in part by grants from the NIH National Cancer Institute CA RO1 64648 (MacEwen), and CA R29 67952 (Radinsky), and a Supplemental Consortium Grant from NIH (Radinsky). The authors thank Richard Grygiel and Erica Wick for their assistance in performing the in vitro procedures.

PY - 2003

Y1 - 2003

N2 - To further characterize the role of hepatocyte growth factor-scatter factor (HGF-SF) and its receptor (c-Met) in osteosarcoma (OS), human OS cell lines with low (SAOS-2) and high (SAOS-LM2) metastatic potential, and cell lines derived from spontaneous canine OS were studied. All cell lines were evaluated for c-Met and HGF-SF expression and receptor activation using Northern, RT-PCR, and Western blot analyses, respectively. Functional activity of receptor-ligand interaction was measured using c-Met phosphorylation status, proliferation assays (anchorage-dependent and -independent), Matrigel invasion, modulation of urokinase plasminogen activator (uPA) expression, and cell dispersion (scattering). All cell lines exhibited steady-state mRNA expression of c-Met. The canine OS cell lines also expressed HGF-SF mRNA as determined by RT-PCR analysis. Western analysis showed c-Met protein expression and HGF-stimulated (human) or constitutive (canine) receptor autophosphorylation. Treatment with recombinant human HGF resulted in enhanced proliferation in 3 of 5 OS cell lines and enhanced colony formation in 2 of 5 OS cell lines. Matrigel invasion was significantly enhanced in 3 of the cell lines and uPA levels were significantly increased in the SAOS-2 cells following HGF treatment. Scattering was enhanced in both the SAOS-2 and SAOS-LM2 cells. These data support the involvement of c-Met and HGF-SF in the growth and progression of human and canine OS, and may offer new targets for the development of therapeutic strategies for OS.

AB - To further characterize the role of hepatocyte growth factor-scatter factor (HGF-SF) and its receptor (c-Met) in osteosarcoma (OS), human OS cell lines with low (SAOS-2) and high (SAOS-LM2) metastatic potential, and cell lines derived from spontaneous canine OS were studied. All cell lines were evaluated for c-Met and HGF-SF expression and receptor activation using Northern, RT-PCR, and Western blot analyses, respectively. Functional activity of receptor-ligand interaction was measured using c-Met phosphorylation status, proliferation assays (anchorage-dependent and -independent), Matrigel invasion, modulation of urokinase plasminogen activator (uPA) expression, and cell dispersion (scattering). All cell lines exhibited steady-state mRNA expression of c-Met. The canine OS cell lines also expressed HGF-SF mRNA as determined by RT-PCR analysis. Western analysis showed c-Met protein expression and HGF-stimulated (human) or constitutive (canine) receptor autophosphorylation. Treatment with recombinant human HGF resulted in enhanced proliferation in 3 of 5 OS cell lines and enhanced colony formation in 2 of 5 OS cell lines. Matrigel invasion was significantly enhanced in 3 of the cell lines and uPA levels were significantly increased in the SAOS-2 cells following HGF treatment. Scattering was enhanced in both the SAOS-2 and SAOS-LM2 cells. These data support the involvement of c-Met and HGF-SF in the growth and progression of human and canine OS, and may offer new targets for the development of therapeutic strategies for OS.

KW - Canine

KW - Hepatocyte growth factor

KW - Human

KW - Invasion

KW - Molecular determinants

KW - Osteosarcoma

KW - Scatter factor

KW - Urokinase plasminogen activator

KW - c-Met

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U2 - 10.1023/A:1025404603315

DO - 10.1023/A:1025404603315

M3 - Article

C2 - 14524531

AN - SCOPUS:0041736272

SN - 0262-0898

VL - 20

SP - 421

EP - 430

JO - Clinical and Experimental Metastasis

JF - Clinical and Experimental Metastasis

IS - 5

ER -

c-Met tyrosine kinase receptor expression and function in human and canine osteosarcoma cells

Abstract

Keywords

ASJC Scopus subject areas

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