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

Research output: Contribution to journalArticle

39 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4729-4738
Number of pages10
JournalCancer Research
Volume55
Issue number20
Publication statusPublished - 1995

Fingerprint

Fibroblast Growth Factor 2
B-Lymphocytes
Growth
Cell Line
Adenocarcinoma
Clone Cells
Fibroblast Growth Factor Receptors
Urokinase-Type Plasminogen Activator
Conditioned Culture Medium
Nude Mice
Protein-Tyrosine Kinases
Cornea
Extracellular Matrix
Actins
Intercellular Signaling Peptides and Proteins
Protein Isoforms
Up-Regulation
Down-Regulation
Complementary DNA
Cell Culture Techniques

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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.

Research output: Contribution to journalArticle

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",
year = "1995",
language = "English",
volume = "55",
pages = "4729--4738",
journal = "Journal of Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "20",

}

TY - JOUR

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.

PY - 1995

Y1 - 1995

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.

UR - http://www.scopus.com/inward/record.url?scp=0028858371&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028858371&partnerID=8YFLogxK

M3 - Article

VL - 55

SP - 4729

EP - 4738

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0008-5472

IS - 20

ER -