Acidic and basic fibroblast growth factors in human breast tissue

doi:10.1016/0959-8049(94)90426-X

European Journal of Cancer

Volume 30, Issue 4, 1994, Pages 496-503

https://doi.org/10.1016/0959-8049(94)90426-X Get rights and content

Abstract

Previously we have reported changes in fibroblast growth factors (FGF) in conditioned medium (CM) derived from rat mammary tumours undergoing remission. We have used a similar approach to assay for the presence of FGFs in human breast tissue and cell lines. The majority of cancer tissues ( $3550$ ), benign tissues ( $89$ ) and all cancer adjacent normal tissues ( $2020$ ) released heat labile, NR6 transforming activity which coeluted from heparin with acidic FGF (aFGF) at 0.9–1.1 M NaCl and was neutralised by antibodies to aFGF. The conclusion that the majority of breast cancers contain active aFGF was supported by immunoblotting. The CM of a minority ( $1550$ ) of cancers and one benign tissue had highly transforming activity for NR6 cells, and was mitogenic for a breast cancer cell line, was heat labile, and strongly heparin binding, eluting at 1.5–2.0 M salt. It was not immunoreactive with antibodies to aFGF, basic FGF (bFGF) or Kaposi's FGF (kFGF) and its activity was reduced by the presence of aFGF, suggesting competition for the same receptor. Very little aFGF was observed in the CM of these tumours, and neither aFGF nor other FGF activity was detected in CM of breast cell lines.

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Citation Excerpt :
Finally, our findings are important because heparin-binding factors have been identified in a broad variety of cancers, including bladder cancer,28 hepatocellular carcinoma,29 pancreatic cancer,30 prostate cancer,31 and breast cancer.32 Among the heparin-binding factors that have been purified from these cancers are vascular endothelial growth factor, fibroblast growth factor, and pleiotrophin.33–38 All of these heparin binding factors seem to promote angiogenesis to some extent, a property that may account for an earlier observation that heparin derived from mast cells promotes endothelial cell proliferation.39
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FGF2 (basic fibroblast growth factor) is a multifunctional growth factor and exhibits diverse function in different cell types. In breast, loss of FGF2 expression is associated with malignant progression. In order to understand the role of FGF2 in maintenance of normal breast structures and control of cell growth, we restored FGF2 expression in the breast cancer cell line MCF-7. The FGF2 retrovirally infected MCF-7 cells (MCF-7.F2.5) not only expressed FGF2 in cytoplasm and nuclei, but also released FGF2 into culture medium both on plastic and in Matrigel conditions. The MCF-7.F2.5 cells formed branches in Matrigel and this effect was abolished by the addition of a neutralising anti-FGF2 antibody or function blocking antibodies to α2, α3 and β1 integrins. Furthermore, MCF-7.F2.5 cells lost their ability for anchorage-independent growth in soft agar. When MCF-7 and MCF-7.F2.5 cells were injected into nude mice, there was a 1.6- to 3.2-fold reduction of tumour volume with MCF-7.F2.5 cells in comparison with the parental MCF-7 cells. MCF-7.F2.5 cells also demonstrated a reduction in oestrogen receptor-α (ERα) both in vitro and in vivo. Our results suggest that introduction of the FGF2 gene into MCF-7 cells altered the malignant tumour cells towards a more benign phenotype in vitro and in vivo.
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Background: We present cytogenetics and fibroblast growth factor immunohistochemistry in one case of cystosarcoma phyllodes with localized disease and one with metastatic spread. The p53 gene was sequenced in the malignant case. Materials and Results: Karyotype analysis used trypsin-Giemsa banding. Immunohistochemistry of FGF1, FGF2, FGFR1 and p53 used avidin-biotin detection of the primary antibody. One case had a mosaic female karyotype and three clones: one normal, one with trisomy 7, and one with both trisomy 5 and a rearranged chromosome 1. In the second case, a resected pulmonary metastasis had the karyotype 43-47,XX,+mar1,+mar2[6]/43-46,XX,+del(7)(p10)[3],+mar2[1][cp3]/46,XX[10]. These tumors expressed FGF1, FGF2, and FGFR1. The malignant case showed immunostaining for p53 protein, but a wild-type gene sequence. Conclusion: The karyotype of cystosarcoma phyllodes is complex, with wide case-to-case variation. These tumors express members of the FGF family. Metastatic behavior can occur in the presence of a wild-type p53 gene.
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PaperAcidic and basic fibroblast growth factors in human breast tissue

Abstract

Trends Biochem Sci

Biochem Biophys Acta

Eur J Cancer

Tamoxifen flare in advanced breast cancer

JAMA

Differential responsiveness of human breast cancer cell lines MCF-7 and T47D to growth factors and 17 beta-estradiol

Cancer Res

Purification and characterisation of a newly identified growth factor specific for epithelial cells

Mesoderm induction in early Xenopus embryos by heparin-binding growth factors

Nature

Amplification of FGF related genes in human tumours: possible involvement of HST in breast cancer

Oncogene

Modulation of plasminogen activator activity in human endometrial adenocarcinoma cells by basic fibroblast growth factor and transforming growth factor beta

Cancer Res

Transforming growth factors from neoplastic and non-neoplastic tissues

A platelet derived growth factor like molecule and reduced expression of platelet derived growth factor receptors accompanying transformation by a wide spectrum of agents

An oncogene isolated by transfection of Kaposi's sarcoma DNA encodes a growth factor that is a member of the FGF family

Cell

Variants of 3T3 cells lacking mitogenic response to epidermal growth factor

Paper
Acidic and basic fibroblast growth factors in human breast tissue