Profile of epidermal growth factor receptor (EGFr) expression in human malignancies: effects of exposure to EGF and its biological influence on established human tumour cell lines.
The aim of this study was to compare the profile of EGFr expression in transitional cell carcinoma of the bladder (TCC) and in oral squamous cell carcinoma (OSCC). In addition, to study the influence of EGF stimulation on the expression of major histocompatibility complex class I antigens, placental alkaline phosphatase (PLAP) as well as changes in tumour cell sensitivity to cisplatin using immunocytochemical staining, a colorimetric assay and SDS-gel electrophoresis. The results showed that: a) strong EGFr expression could be seen in 22/88 (27%) cases of TCCs. In oral tumours the values for non-invasive ameloblastoma and invasive OSCC were 4/25 (16%) and 30/41 (73%) respectively. b) EGFr expression in tumour cell lines paralleled that of tumour biopsies. The number of lines expressing high and low EGFr expression amongst TCCs were 4 and 4 and in OSCCs were 3 and 1 respectively. c) Exposure of tumour cell lines to EGF led to: i) an increase in EGFr expression (stimulatory indices SI, ranged from 1.06 to 2.58) for TCCs but a decrease in the case of OSCCs (SI ranged from 0.01 to 0.85). The corresponding SI values for class I antigens were 0.95-1.16 and 0.10-0.84. ii) A significant reduction in expression of PLAP by OSCC cell lines. iii) An increased susceptibility of OSCC cell lines to cisplatin by as much as 14% (p<0.001). These data demonstrated the overexpression of EGFr in a significant proportion of TCCs. As for oral tumours it depended on whether they were of an invasive or non-invasive type. In the invasive cases the majority overexpressed EGFr. The exposure of OSCC but not TCC tumour cells to EGF resulted in down regulation of EGFr and class I antigens. The expression of PLAP was also significantly reduced. Exposure of OSCC cells to EGF resulted in their increased susceptibility to cisplatin. The data supports the notion that the mitogenic activation of some tumour cells by EGF resulted in a reduction of their immune visibility, differentiation status and an increase in chemosensitivity.
Nouri
A M
AM
Uro/Oncology Research Unit, The Royal London Medical College, London E1 1BB, UK. a.nouri@mds.qmw.ac.uk
Thompson
C
C
Cannell
H
H
Symes
M
M
Purkiss
S
S
Amirghofran
Z
Z
D000469:Alkaline Phosphatase / Q000096:biosynthesis / Q000187:drug effects; D000970:Antineoplastic Agents / Q000494:pharmacology; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000187:drug effects; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010920:Placenta / Q000201:enzymology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D015395:Histocompatibility Antigens Class I; D007527:Isoenzymes; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D000469:Alkaline Phosphatase; D002945:Cisplatin