The effects of platelet-derived growth factor and receptor on normal and neoplastic human ovarian surface epithelium.
Several growth factors have been shown to stimulate or inhibit the growth of human ovarian surface epithelial (HOSE) cells. Platelet-derived growth factor (PDGF) is likely to be released onto the ovarian surface epithelium during follicular wound repair. We undertook the evaluation of this factor and its receptor in normal and malignant ovarian cells.


OBJECTIVE
The goal of this study was to evaluate the response of HOSE cells to PDGF in vitro and identify PDGF receptors on normal and malignant ovarian epithelial cells. In addition, we wanted to examine the prognostic value of the PDGF receptors in clinical specimens.


METHODS
Normal HOSE cells were cultured and growth response to PDGF assayed by 3H uptake. PDGF receptor status on HOSE cells, established ovarian carcinoma cell lines, and paraffin tissue was performed by immunohistologic techniques. Data on ovarian cancer patients relapse-free survival (RFS) were abstracted from the Lankenau Hospital Tumor Registry and RFS was plotted using the Kaplan-Meier method.


RESULTS
HOSE cells increased 3H uptake in a dose-dependent manner in response to PDGF. HOSE cells stain positively for both alpha and beta receptors, as does the chemotherapy naive cell line A2780. The platinum-resistant CP30 cell line loses PDGF alpha staining. Of 21 ovarian cancer specimens, only 1 retained PDGF alpha receptors while 8 retained PDGF beta receptors. Those patients positive for PDGF receptor beta had a significantly longer relapse-free survival than PDGF beta receptor-negative patients.


CONCLUSIONS
PDGF enhances the growth of HOSE cells in vitro and may play a role in ovarian cancer development. Patients whose tumors retain PDGF receptor beta staining positivity have a prolonged relapse-free survival.
Lankenau Hospital and Medical Research Center, 100 Lancaster Avenue, Wynnewood, Pennsylvania 19096, USA.
M B
MB
Dabrow
M R
MR
Francesco
F X
FX
McBrearty
S
S
Caradonna
D002455:Cell Division; D002478:Cells, Cultured; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D010053:Ovary / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D010982:Platelet-Derived Growth Factor; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor; D013936:Thymidine