Growth advantage and vascularization induced by basic fibroblast growth factor overexpression in endometrial HEC-1-B cells: An export-dependent mechanism of action
D. Coltrini, A. Gualandris, E. E. Nelli, S. Parolini, M. P. Molinari-Tosatti, N. Quarto, M. Ziche, R. Giavazzi, M. Presta
Istituto di Ricerche Farmacologiche "Mario Negri"
The human endometrial adenocarcinoma HEC-1-B cell line was transfected with an expression vector harboring the human basic fibroblast growth factor (bFGF) cDNA under the control of the human β-actin gene promoter. Stable transfectants were obtained in which a constitutive, limited overexpression of M(r) 24,000, 22,000, and 18,000 bFGF isoforms was observed. When transfectants were screened for the capacity to release the growth factor, significant amounts of bFGF were present in the conditioned medium and extracellular matrix of the bFGF-B9 clone but not of the bFGF-A8 clone, even though both cell lines produced similar levels of intracellular bFGF. When compared to parental cells, bFGF-B9 cells showed down-regulation of tyrosine kinase fibroblast growth factor receptors along with up-regulation of urokinase-type plasminogen activator expression which was abolished by incubation of the cell cultures with neutralizing anti-bFGF antibody. In vivo, bFGF-B9 cells formed highly vascularized tumors growing faster than parental cells when injected s.c. in nude mice. Also, they were more potent than nontransfected cells in inducing an angiogenic response in the rabbit cornea assay. In contrast, the bFGF-A8 cell phenotype was indistinguishable from parental cells both in vitro and in vivo. In conclusion, clonal differences exist within the HEC-1-B cell line in the capacity to release bFGF. bFGF export by human endometrial adenocarcinoma cells results in autocrine and paracrine effects that confer a growth advantage in vivo associated with increased neovascularization.
Fibroblast Growth Factor 2
B-Lymphocytes
Fibroblast Growth Factor Receptors
Conditioned Culture Medium
Protein-Tyrosine Kinases
Protein Isoforms
Complementary DNA
Coltrini, D., Gualandris, A., Nelli, E. E., Parolini, S., Molinari-Tosatti, M. P., Quarto, N., ... Presta, M. (1995). Growth advantage and vascularization induced by basic fibroblast growth factor overexpression in endometrial HEC-1-B cells: An export-dependent mechanism of action. Cancer Research, 55(20), 4729-4738.
Growth advantage and vascularization induced by basic fibroblast growth factor overexpression in endometrial HEC-1-B cells : An export-dependent mechanism of action. / Coltrini, D.; Gualandris, A.; Nelli, E. E.; Parolini, S.; Molinari-Tosatti, M. P.; Quarto, N.; Ziche, M.; Giavazzi, R.; Presta, M.
In: Cancer Research, Vol. 55, No. 20, 1995, p. 4729-4738.
Coltrini, D, Gualandris, A, Nelli, EE, Parolini, S, Molinari-Tosatti, MP, Quarto, N, Ziche, M, Giavazzi, R & Presta, M 1995, 'Growth advantage and vascularization induced by basic fibroblast growth factor overexpression in endometrial HEC-1-B cells: An export-dependent mechanism of action', Cancer Research, vol. 55, no. 20, pp. 4729-4738.
Coltrini D, Gualandris A, Nelli EE, Parolini S, Molinari-Tosatti MP, Quarto N et al. Growth advantage and vascularization induced by basic fibroblast growth factor overexpression in endometrial HEC-1-B cells: An export-dependent mechanism of action. Cancer Research. 1995;55(20):4729-4738.
Coltrini, D. ; Gualandris, A. ; Nelli, E. E. ; Parolini, S. ; Molinari-Tosatti, M. P. ; Quarto, N. ; Ziche, M. ; Giavazzi, R. ; Presta, M. / Growth advantage and vascularization induced by basic fibroblast growth factor overexpression in endometrial HEC-1-B cells : An export-dependent mechanism of action. In: Cancer Research. 1995 ; Vol. 55, No. 20. pp. 4729-4738.
@article{ef3b797b604c410bb8f6b0206acb8168,
title = "Growth advantage and vascularization induced by basic fibroblast growth factor overexpression in endometrial HEC-1-B cells: An export-dependent mechanism of action",
abstract = "The human endometrial adenocarcinoma HEC-1-B cell line was transfected with an expression vector harboring the human basic fibroblast growth factor (bFGF) cDNA under the control of the human β-actin gene promoter. Stable transfectants were obtained in which a constitutive, limited overexpression of M(r) 24,000, 22,000, and 18,000 bFGF isoforms was observed. When transfectants were screened for the capacity to release the growth factor, significant amounts of bFGF were present in the conditioned medium and extracellular matrix of the bFGF-B9 clone but not of the bFGF-A8 clone, even though both cell lines produced similar levels of intracellular bFGF. When compared to parental cells, bFGF-B9 cells showed down-regulation of tyrosine kinase fibroblast growth factor receptors along with up-regulation of urokinase-type plasminogen activator expression which was abolished by incubation of the cell cultures with neutralizing anti-bFGF antibody. In vivo, bFGF-B9 cells formed highly vascularized tumors growing faster than parental cells when injected s.c. in nude mice. Also, they were more potent than nontransfected cells in inducing an angiogenic response in the rabbit cornea assay. In contrast, the bFGF-A8 cell phenotype was indistinguishable from parental cells both in vitro and in vivo. In conclusion, clonal differences exist within the HEC-1-B cell line in the capacity to release bFGF. bFGF export by human endometrial adenocarcinoma cells results in autocrine and paracrine effects that confer a growth advantage in vivo associated with increased neovascularization.",
author = "D. Coltrini and A. Gualandris and Nelli, {E. E.} and S. Parolini and Molinari-Tosatti, {M. P.} and N. Quarto and M. Ziche and R. Giavazzi and M. Presta",
journal = "Journal of Cancer Research",
publisher = "American Association for Cancer Research Inc.",
T1 - Growth advantage and vascularization induced by basic fibroblast growth factor overexpression in endometrial HEC-1-B cells
T2 - An export-dependent mechanism of action
AU - Coltrini, D.
AU - Gualandris, A.
AU - Nelli, E. E.
AU - Parolini, S.
AU - Molinari-Tosatti, M. P.
AU - Quarto, N.
AU - Ziche, M.
AU - Giavazzi, R.
AU - Presta, M.
N2 - The human endometrial adenocarcinoma HEC-1-B cell line was transfected with an expression vector harboring the human basic fibroblast growth factor (bFGF) cDNA under the control of the human β-actin gene promoter. Stable transfectants were obtained in which a constitutive, limited overexpression of M(r) 24,000, 22,000, and 18,000 bFGF isoforms was observed. When transfectants were screened for the capacity to release the growth factor, significant amounts of bFGF were present in the conditioned medium and extracellular matrix of the bFGF-B9 clone but not of the bFGF-A8 clone, even though both cell lines produced similar levels of intracellular bFGF. When compared to parental cells, bFGF-B9 cells showed down-regulation of tyrosine kinase fibroblast growth factor receptors along with up-regulation of urokinase-type plasminogen activator expression which was abolished by incubation of the cell cultures with neutralizing anti-bFGF antibody. In vivo, bFGF-B9 cells formed highly vascularized tumors growing faster than parental cells when injected s.c. in nude mice. Also, they were more potent than nontransfected cells in inducing an angiogenic response in the rabbit cornea assay. In contrast, the bFGF-A8 cell phenotype was indistinguishable from parental cells both in vitro and in vivo. In conclusion, clonal differences exist within the HEC-1-B cell line in the capacity to release bFGF. bFGF export by human endometrial adenocarcinoma cells results in autocrine and paracrine effects that confer a growth advantage in vivo associated with increased neovascularization.
AB - The human endometrial adenocarcinoma HEC-1-B cell line was transfected with an expression vector harboring the human basic fibroblast growth factor (bFGF) cDNA under the control of the human β-actin gene promoter. Stable transfectants were obtained in which a constitutive, limited overexpression of M(r) 24,000, 22,000, and 18,000 bFGF isoforms was observed. When transfectants were screened for the capacity to release the growth factor, significant amounts of bFGF were present in the conditioned medium and extracellular matrix of the bFGF-B9 clone but not of the bFGF-A8 clone, even though both cell lines produced similar levels of intracellular bFGF. When compared to parental cells, bFGF-B9 cells showed down-regulation of tyrosine kinase fibroblast growth factor receptors along with up-regulation of urokinase-type plasminogen activator expression which was abolished by incubation of the cell cultures with neutralizing anti-bFGF antibody. In vivo, bFGF-B9 cells formed highly vascularized tumors growing faster than parental cells when injected s.c. in nude mice. Also, they were more potent than nontransfected cells in inducing an angiogenic response in the rabbit cornea assay. In contrast, the bFGF-A8 cell phenotype was indistinguishable from parental cells both in vitro and in vivo. In conclusion, clonal differences exist within the HEC-1-B cell line in the capacity to release bFGF. bFGF export by human endometrial adenocarcinoma cells results in autocrine and paracrine effects that confer a growth advantage in vivo associated with increased neovascularization.
JO - Journal of Cancer Research
JF - Journal of Cancer Research