Abstract
The effect of epidermal growth factor (EGF) on the biological behaviour of human tumours in vivo is still controversial. We investigated the effect of EGF on the growth of an EGF receptor-hyperproducing human epidermoid carcinoma, A431 tumour, and on a human small-cell lung carcinoma, H69 tumour, without detectable EGF receptor by using sialoadenectomised (sialex) mice as an endogenous EGF-suppressed animal model. The plasma EGF concentration in the sialex athymic mice was significantly lower than that in the sham-operated mice (P < 0.05). After exogenous EGF replacement with an implanted minipump, the plasma EGF concentration was significantly increased in both groups (P < 0.05). There was no significant difference between the body weight growth curves of sialex and sham-operated mice with and without EGF treatment. The tumour weight of A431, both estimated and measured in sialex mice, was significantly lower than that in sham-operated control mice (P < 0.05), and the growth of A431 tumour was significantly increased by exogenous EGF treatment (P < 0.05). Mitotic activity of these tumours detected by immunohistochemical staining for incorporated bromodeoxyuridine indicated a mitosis-stimulatory effect of endogenous and exogenous EGF on A431 tumours. In contrast to these findings on A431 tumours, a growth-stimulatory effect of endogenous and exogenous EGF was not observed in the H69 tumour. These results suggest a growth-promoting effect of physiological levels of endogenous EGF on EGF receptor-hyperproducing human tumours in vivo.
Highlights
We investigated the effect of endogenous epidermal growth factor (EGF) on EGFhyperproducing human tumours using sialoadenectomised mice
The human epidermoid carcinoma cell line A43 l was obtained from the Japan Cancer Research Resource Bank
After the exogenous EGF replacement, there was no significant difference between the plasma EGF levels of the sialex (7.90± 1.81 ngmJ- 1) and sham-operated mice (8.67± l.54ngmJ- 1) (Figure I)
Summary
Mouse submandibular gland EGF was obtained from Toyobo (Osaka, Japan). Bromodeoxyuridine (BrdU) and anti-BrdU monoclonal antibodies were obtained from Ikeda (Osaka) and Becton Dickinson (Mountain View, CA, USA), respectively. Normal mouse IgG was obtained from Sigma (St Louis, MO, USA). Alzet mini-osmotic pumps were obtained from Alza (Palo Alto, CA, USA). 1251-labelled EGF (100 μCi μg- 1) was purchased from Amersham International (Buckinghamshire, UK). All other reagents were of analytical grade
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