Importance of transforming growth factor alpha/epidermal growth factor receptor autocrine growth mechanism in an ovarian cancer cell line in vivo.
We have elucidated the importance of a transforming growth factor (TGF) alpha and epidermal growth factor receptor autocrine mechanism on the growth of a human ovarian serous cystadenocarcinoma-derived cell line (SHIN-3) in vitro. In this study, we studied the biological significance of this autocrine mechanism in vivo using female athymic nude (nu/nu) mice. We measured the mouse plasma epidermal growth factor and TGF alpha levels by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Plasma epidermal growth factor concentrations were remarkably decreased by sialoadenectomy (Sx): 410 +/- 65 (SE) pg/ml (n = 10) in intact animals; and undetectable in Sx mice (n = 5). Plasma TGF alpha levels were 90 and 40 pg/ml in intact and in Sx animals, respectively. Ten million SHIN-3 cells inoculated into nu/nu mice formed tumors in 100% of mice, and tumors grew progressively. Implantabilities and tumor growth rates of inoculated cells were not affected by Sx and even by Sx and anti-mouse epidermal growth factor antibody treatment. However, anti-TGF alpha monoclonal antibody (mAb) administered to SHIN-3 cell-inoculated Sx animals drastically reduced the tumor growth. Although 10(7) SHIN-3 cells formed tumors in this group, tumor growth was significantly inhibited by 10 micrograms of anti-TGF alpha mAb given 3 times a week, and growth inhibitions were more by 20 micrograms of anti-TGF alpha mAb. Moreover, as aggressive tumor growth as that in Sx animals was resumed by the cessation of anti-TGF alpha mAb treatments. All these data suggested the biological importance of a TGF alpha/epidermal growth factor receptor autocrine mechanism on the growth of this cell line in vivo.
Department of Obstetrics and Gynecology, Osaka University Medical School, Japan.
H
H
Kurachi
K
K
Morishige
K
K
Amemiya
H
H
Adachi
K
K
Hirota
A
A
Miyake
O
O
Tanizawa
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D002455:Cell Division; D002460:Cell Line; D003537:Cystadenoma / Q000473:pathology* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor / Q000032:analysis; D066246:ErbB Receptors / Q000502:physiology*; D005260:Female; D006801:Humans; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000473:pathology* / Q000503:physiopathology; D011863:Radioimmunoassay; D016211:Transforming Growth Factor alpha / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors