Serially heterotransplanted human prostate tumours as an experimental model

Abstract

Preclinical research on prostate cancer (PC) therapies uses several models to represent the human disease accurately. A common model uses patient prostate tumour biopsies to develop a cell line by serially passaging and subsequent implantation, in immunodeficient mice. An alternative model is direct implantation of patient prostate tumour biopsies into immunodeficient mice, followed by serial passage in vivo. The purpose of this review is to compile data from the more than 30 years of human PC serial heterotransplantation research. Serially heterotransplanted tumours are characterized by evaluating the histopathology of the resulting heterotransplants, including cellular differentiation, karyotype, marker expression, hormone sensitivity, cellular proliferation, metastatic potential and stromal and vascular components. These data are compared with the initial patient tumour specimen and, depending on available information, the patient’s clinical outcome was compared with the heterotransplanted tumour. The heterotansplant model is a more accurate preclinical model than older generation serially passaged or genetic models to investigate current and newly developed androgen-deprivation agents, antitumour compounds, anti-angiogenic drugs and positron emission tomography radiotracers, as well as new therapeutic regimens for the treatment of PC.

Experimental models for the development of new medical treatments in prostate cancer

“…Second, the fidelity with which the heterotransplant model reproduces the clinical outcome observed in patients must be characterized. This defines the predictive value of the heterotransplant model which ultimately has to predict how human beings will respond to newly developed therapies (1).…”

Discrepancies between metabolic activity and DNA content as tool to assess cell proliferation in cancer research

“…It was shown that metabolic activity varied greatly with cell density and did not correlate in a linear fashion. High cell densities are also a feature in cancer research, where cancer cell lines are frequently used for experiments [9]. These cell lines typically proliferate rapidly and reach high cell densities over a short period of time; especially in 2D cultures [10].…”