The rat endometrial adenocarcinoma cell line RUCA-I: a novel hormone-responsive in vivo/in vitro tumor model.
The recently established, estrogen receptor positive rat endometrial adenocarcinoma cell line RUCA-I was tested for estrogen responsiveness in vivo and in vitro. In vivo, 10(6) RUCA-I cells were injected subcutaneously into intact, ovariectomized, or ovariectomized, estradiol-substituted syngenic DA/Han rats. All animals developed well differentiated endometrial adenocarcinoma, that had metastasized to peripheral lymph nodes and into the lung. Ovariectomy reduced tumor and lymph node weight, as well as number of lung metastases significantly compared to controls. In another series of experiments, treatment with the pure anti-estrogen ZK 119010 basically gave the same results as seen in ovariectomized animals, whereas tamoxifen treatment had no effect on metastasis of RUCA-I cells. These findings clearly demonstrate the estrogen dependency of growth and metastasis of RUCA-I cells in vivo. In vitro, we assessed the estrogenic and anti-estrogenic potency of various anti-estrogens, thereby investigating their effects on the expression of components of the complement C3 complex as an estradiol-induced protein and on the expression of fibronectin as an estrogen-repressed protein. Evaluating the relative anti-estrogenic potency of these anti-estrogens we found that ICI 164384 and ICI 182780 behaved as complete antagonists in vitro. Tamoxifen, like estradiol, stimulated complement C3 production and repressed fibronectin expression and has to be regarded as an agonist in this particular in vitro system. ZK 119010 if given alone had no significant influence on the biosynthesis of complement C3 and of fibronectin if compared to the unstimulated control. In addition, another estrogen dependent parameter was identified. Estrogen and anti-estrogen treatment affected glycosylation of complement C3 components. After estradiol treatment predominantly the higher glycosylated epitope of complement C3 became detectable, which could be transformed into the low molecular weight epitope by treatment with hyaluronidase. Finally, we compared the anti-proliferative effects of ICI 164384 and of tamoxifen in vitro. Both anti-estrogens slightly inhibited the growth of RUCA-I rat endometrial adenocarcinoma cells. In conclusion, RUCA-I cells represent a powerful, endometrial derived experimental model to test the agonistic and antagonistic properties of anti-estrogens on growth and metastasis in vivo and on gene expression in vitro. The effects of the tested anti-estrogens on gene expression of RUCA-I cells were found to be useful in predicting their effectiveness on tumor growth in vivo.
Vollmer
G
G
Institut für Biochemische Endokrinologie, Medizinische Universität zu Lübeck, Germany.
Schneider
M R
MR
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003176:Complement C3 / Q000096:biosynthesis / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000939:Epitopes / Q000032:analysis; D004958:Estradiol / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D004967:Estrogens / Q000502:physiology; D005260:Female; D005353:Fibronectins / Q000096:biosynthesis / Q000378:metabolism; D006031:Glycosylation; D006821:Hyaluronoglucosaminidase; D008175:Lung Neoplasms / Q000556:secondary; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000378:metabolism; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010052:Ovariectomy; D051381:Rats; D014407:Tumor Cells, Cultured
D003176:Complement C3; D000939:Epitopes; D004965:Estrogen Antagonists; D004967:Estrogens; D005353:Fibronectins; D009363:Neoplasm Proteins; D004958:Estradiol; D006821:Hyaluronoglucosaminidase