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[Hormone dependence of malignant ovarian tumors--an in vitro model]
K Schieder1, C Bieglmayer, H Kölbl
1II. Univ.-Frauenklinik Wien.
Abstract:
The steroid hormone receptor content of 32 malignant ovarian tumors was compared with the in vitro effectiveness of 4 hydroxytamoxifen (OH-TAM) and medroxy-progesterone acetate (MPA) tested in the Human Tumor Colony Forming Assay (HTCFA). The sensitivity for the receptor determination was 5 fmol/mg cytosol protein. Estrogen receptors (ER) and progesterone receptors (PR) were found in 15 (47%) and 13 (41%) of the tumors respectively. As standard criteria for the HTCFA, a minimum of 30 colonies with a diameter of more than 60 microns and 100 microns was used in the control group. The in-vitro sensitivity of ovarian tumors to OH-TAM and MPA was independent on the ER or PR content, and amounted to 9% for OH-TAM and 6% for MPA. However, all 12 ER-PR-tumors proved resistant to OH-TAM and MPA. 18 ovarian tumors showed a sufficient colony growth, even in the size class exceeding 100 microns. With a minimum colony size of 60 microns and 100 microns, 17% and 33% respectively were sensitive to OH-TAM. A similar effect on the proliferative capacity of the Tumor Colony Forming Units (TCFUs), unrelated to PR, was observed with MPA. Dependent on colony size, we found an increasing sensitivity against MPA from 11% to 22%. The in-vitro effectiveness of both OH-TAM and MPA in the clonogenic assay of malignant ovarian tumors was certainly not as potent as suggested by the results obtained in biochemical steroid hormone receptor analysis. To prove the hormonal response in the HTCFA, it is necessary to determine number and size of the colonies as an expression of their proliferative potential.
Insights
This study found that while estrogen receptors (ER) and progesterone receptors (PR) are present in ovarian tumors, their levels do not predict in vitro effectiveness of 4-hydroxytamoxifen (OH-TAM) and medroxy-progesterone acetate (MPA) in the Human Tumor Colony Forming Assay (HTCFA). Tumor sensitivity to these hormones varied and was not solely dependent on receptor content.
Area of Science:
- Oncology
- Endocrinology
- Pharmacology
Context:
- Malignant ovarian tumors exhibit variable steroid hormone receptor content.
- Assessing in vitro drug sensitivity is crucial for personalized cancer treatment.
Purpose:
- To compare steroid hormone receptor levels in ovarian tumors with their in vitro sensitivity to 4-hydroxytamoxifen (OH-TAM) and medroxy-progesterone acetate (MPA) using the Human Tumor Colony Forming Assay (HTCFA).
Summary:
- Estrogen receptors (ER) and progesterone receptors (PR) were detected in 47% and 41% of ovarian tumors, respectively. In vitro sensitivity to OH-TAM and MPA was largely independent of ER/PR content, with tumors lacking both receptors showing complete resistance.
- Tumor sensitivity to OH-TAM and MPA varied based on colony size criteria in the HTCFA, with higher sensitivity observed for larger colonies (≥100 microns).
- The in vitro effectiveness of OH-TAM and MPA in the clonogenic assay was less potent than suggested by biochemical receptor analysis, highlighting the importance of assessing proliferative capacity via colony number and size.
Impact:
- Findings suggest that standard steroid hormone receptor analysis alone may be insufficient for predicting response to hormonal therapies in ovarian cancer.
- The Human Tumor Colony Forming Assay (HTCFA), considering colony number and size, offers a more comprehensive method for evaluating in vitro hormonal response in ovarian tumors.
- This research may inform the development of more accurate predictive biomarkers and treatment strategies for ovarian cancer patients.