Stimulation of human tumor xenograft growth by local estrogen biosynthesis in stromal cells.
BACKGROUND
Both biochemical and histochemical studies have demonstrated the expression of aromatase activity in stromal cells surrounding breast cancers, suggesting that local estrogen biosynthesis promotes the growth of these cancers. However, the role of local aromatase activity in stimulating hormone-dependent breast cancer is still controversial.


METHODS
A hormone-dependent human breast carcinoma xenograft, Br-10 and human fibroblast cells obtained from a patient with benign breast disease were used in the experiments. When subcutaneously inoculated Br-10 started exponential growth in female nude mice, 10(6) fibroblast cells were injected around the tumor with or without intramuscular administration of 50 mg/kg testosterone.


RESULTS
The growth of Br-10 treated with fibroblasts and testosterone was significantly enhanced in comparison with the control (p < 0.05). This stimulation by fibroblasts and testosterone was also observed in ovariectomized nude mice. Immunohistochemical staining for aromatase was observed in tumor sections containing Br-10 from mice treated with fibroblasts and testosterone, particularly around the carcinomatous glands.


CONCLUSIONS
We conclude that estrogen produced locally by aromatase in fibroblasts can regulate the growth of hormone-dependent breast carcinoma cells.
Department of Surgery, Social Insurance Saitama Chuo Hospital, Japan.
J
J
Koh
T
T
Kubota
H
H
Sasano
M
M
Hashimoto
Y
Y
Hosoda
M
M
Kitajima
D000818:Animals; D001141:Aromatase / Q000032:analysis; D001941:Breast Diseases / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D010052:Ovariectomy; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D014183:Transplantation, Heterologous
D004967:Estrogens; D013739:Testosterone; C004648:testosterone enanthate; D001141:Aromatase