A paracrine role for myoepithelial cell-derived FGF2 in the normal human breast.
We have studied separated normal human breast epithelial and myoepithelial cells for the presence of basic fibroblast growth factor (FGF2) and its receptors, both low (heparan sulfate proteoglycans) and high affinity (FGFR1), and for the effects of FGF2 on the proliferation of both cell types. Our results indicate that these cells differ markedly in their synthesis and response to FGF2. We found, using PCR of purified cell populations, mRNA for FGF2 only in the myoepithelial cells, whereas immunostaining and Western blotting results demonstrated the presence of FGF2 protein in both epithelial and myoepithelial cells. FGF2 had no effect on the proliferation of myoepithelial cells, but it did maintain the survival of the separated epithelial cells in low serum and stimulate their growth in 5% and 10% FCS. Immunostainable FGFR1 was present in epithelial cells and, to a lesser extent, in myoepithelial cells. Low-affinity binding sites for FGF2 were synthesized by epithelial and myoepithelial cells, but myoepithelial cells possessed a greater proportion of higher-affinity heparan sulfate proteoglycans. These results indicate that myoepithelial cell-derived FGF2 may be an important paracrine factor controlling epithelial cell survival and growth in the normal human breast.
Gomm
J J
JJ
Cancer Research Campaign Department of Medical Oncology, Charing Cross and Westminster Medical School, London, United Kingdom.
Browne
P J
PJ
Coope
R C
RC
Bansal
G S
GS
Yiangou
C
C
Johnston
C L
CL
Mason
R
R
Coombes
R C
RC
D015139:Blotting, Southern; D015153:Blotting, Western; D001940:Breast / Q000166:cytology*; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D004847:Epithelial Cells; D004848:Epithelium / Q000737:chemistry / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005944:Glucosamine / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008934:Mitogens / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis* / Q000235:genetics; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis* / Q000235:genetics; D013347:Subcellular Fractions / Q000737:chemistry; D013778:Tetrazolium Salts; D014316:Tritium
D017931:DNA Primers; D008934:Mitogens; D017468:Receptors, Fibroblast Growth Factor; D013778:Tetrazolium Salts; D014316:Tritium; D016222:Fibroblast Growth Factor 2; C496353:FGFR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D005944:Glucosamine