Production of VEGF and expression of the VEGF receptors Flt-1 and KDR in primary cultures of epithelial and stromal cells derived from breast tumours.
Production of vascular endothelial growth factor (VEGF) and expression of its receptors Flt-1 and KDR was determined in primary cultures of separated epithelial and stromal-enriched cultures derived from ten primary human breast carcinomas. By enzyme-linked immunosorbent assay, epithelial cells produced a mean VEGF of 33 +/- 7 pg ml(-1) microg(-1) RNA (range 11-70). Stromal cells produced similar levels, with a mean of 48 +/- 11 pg ml(-1) microg(-1) RNA (range 7-92). This was significantly greater than the amount produced by similar cultures derived from normal breast tissue (epithelial mean 19 +/- 5 pg ml(-1) microg(-1) RNA, range 9-34, P < 0.05 vs tumour epithelial culture; stromal mean 26 +/- 8 pg ml(-1) microg(-1) RNA, range 3-56). Flt-1 and KDR receptors were analysed by semi-quantitative reverse transcription polymerase chain reaction. Flt-1 was expressed by four of six epithelial and five of six stromal cultures. When expressed by both cell types, Flt-1 appeared to be significantly more abundant on stromal cells compared with epithelial cultures. Only a single tumour, a lobular carcinoma, failed to express Flt-1 on either cell type. With KDR, the reverse was true with constitutive expression of this receptor by epithelial cultures and zero or reduced (3/6) expression by stromal cultures. Differences in the expression pattern of VEGF receptors may reflect a differential response to VEGF by specific cell types. Thus, production of VEGF and expression of VEGF receptors Flt-1 and KDR by breast cancer epithelial and stromal cells suggests that VEGF may fulfil not only an angiogenic role, but also play a fundamental role as an autocrine/paracrine regulator in breast cancer, thereby facilitating tumour proliferation and subsequent invasion.
Speirs
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V
Department of Medicine, University of Hull, UK.
Atkin
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SL
D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D018929:Cell Culture Techniques; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology; D008222:Lymphokines / Q000096:biosynthesis*; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D017978:Receptors, Growth Factor / Q000096:biosynthesis*; D040262:Receptors, Vascular Endothelial Growth Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D015850:Interleukin-6; D016209:Interleukin-8; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1