Coexpression of granulocyte colony stimulating factor and its receptor in primary ovarian carcinomas.
Immunohistochemistry was used to determine the expression of granulocyte colony-stimulating factor (G-CSF) and its receptor (G-CSFR) in primary ovarian carcinomas. The expression of G-CSFR was observed in the malignant cells of each of the 46 primary carcinomas examined; G-CSF was coexpressed in both the malignant epithelial cells and the stroma of 56.5% of the specimens. Thus the majority of ovarian carcinomas harbor both potential autocrine and paracrine G-CSF axes. In 37% of the samples, G-CSF was expressed only within stromal cells, suggesting that only a potential paracrine system is in place. In a preliminary, retrospective, evaluation, the survival of patients whose tumors expressed only the apparent paracrine loop was significantly worse than patients whose tumors expressed both potential autocrine and paracrine G-CSF-based regulatory loops (14.5 vs. 42.5 months, respectively). Studies on the potential function of G-CSF were performed using the G-CSFR-expressing OVCAR-3 ovarian carcinoma line. As a single agent, rhG-CSF failed to stimulate [3H]-thymidine incorporation in these cells, but enhanced the mitogenic action of epidermal growth factor (EGF) in a dose-dependent manner. Thus, potential autocrine and/or paracrine loops involving G-CSF and its receptor occur in over 90% of primary ovarian carcinomas, and may act to modulate the action of growth factors.
Savarese
T M
TM
Cytokine/Cytokine Receptor Laboratory, LINK Laboratories, UMass Cancer Center, University of Massachusetts Medical School, Worcester, MA 01655, USA. todd.savarese@umassmed.edu
Mitchell
K
K
McQuain
C
C
Campbell
C L
CL
Guardiani
R
R
Wuu
J
J
Ollari
C
C
Reale
F
F
Nelson
B E
BE
Chen
A
A
Quesenberry
P J
PJ
D002470:Cell Survival / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000032:analysis* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000473:pathology; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000032:analysis*; D011994:Recombinant Proteins; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D004815:Epidermal Growth Factor; D013936:Thymidine