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Androgen-dependent human prostate cancer in nude mice. The PC-82 tumor model
G J van Steenbrugge1, F H Schröder
1Department of Urology, Erasmus University Rotterdam, The Netherlands.
Abstract:
Permanent transplantable human tumors in nude mice offer the possibility of studying the impact of different (endocrine) treatment regimens on human cancer tissue. Among the limited number of human tumor models in athymic nude mice developed so far, the PC-82 tumor (which was established in our institution) mimics many of the important properties of clinical prostate cancer. The absence of PC-82 tumor growth in intact female and in castrated male mice indicates the absolute requirement of androgen for the growth of this tumor. Delayed testosterone (T) substitution (up to 70 days after tumor grafting) in PC-82 transplanted female mice resulted in tumor growth. This indicated that after androgen withdrawal at least part of the cells do not die and keep the capability to respond to androgens. Androgen withdrawal from T-implanted tumor-bearing female mice caused a rapid reduction (90% within 1 day) of the tissue T and a slower decline (up to 90% within 7-10 days) of tissue DHT concentrations. By the use of Silastic implants, containing different proportions of T mixed with cholesterol, circulating T levels of 0.2-20 nmol/L were obtained. It was observed that a constant plasma T level between 1 and 2 nmol/L (achieved with 10% T implants) is the threshold below which growth of the PC-82 tumor tissue is no longer stimulated.
Insights
The PC-82 human prostate cancer model in nude mice requires androgens for growth. A threshold plasma testosterone level between 1-2 nmol/L is necessary to stimulate PC-82 tumor growth.
Area of Science:
- Oncology
- Endocrinology
- Animal Models
Background:
- Permanent transplantable human tumors in nude mice are valuable for studying cancer treatment.
- The PC-82 tumor model closely resembles clinical prostate cancer.
- PC-82 tumor growth is dependent on androgens.
Purpose of the Study:
- To investigate the androgen dependency of the PC-82 human prostate cancer model in vivo.
- To determine the threshold level of testosterone required for PC-82 tumor growth stimulation.
Main Methods:
- Utilized PC-82 tumor xenografts in athymic nude mice.
- Administered testosterone (T) via Silastic implants to achieve varying circulating T levels (0.2-20 nmol/L).
- Monitored tumor growth in response to different androgen levels and withdrawal.
Main Results:
- PC-82 tumor growth was absent in intact females and castrated males, confirming absolute androgen requirement.
- Delayed testosterone substitution supported tumor growth, indicating cell survival after androgen withdrawal.
- Androgen withdrawal led to rapid tissue testosterone and slower dihydrotestosterone (DHT) decline.
- A plasma testosterone level of 1-2 nmol/L was identified as the threshold for stimulating PC-82 tumor growth.
Conclusions:
- The PC-82 tumor model is a robust in vivo model for studying prostate cancer androgens.
- Androgen withdrawal does not cause complete cell death, preserving responsiveness to androgens.
- Specific circulating testosterone levels are critical for regulating the growth of this human prostate cancer xenograft.