Small-cell neuroendocrine carcinoma of the prostate: are heterotransplants a better experimental model?

Abstract

Small-cell neuroendocrine carcinoma of the prostate (SCNCP) is an uncommon type of prostate cancer. However, it is of clinical importance because it is one of the most aggressive tumors of the prostate with a very poor prognosis. There exist few artificially cultured tumor cell lines to study SCNCP. Then, another approach to that study consists in the use of fresh tumor tissue obtained from patients and its heterotransplantation into host mice. The purpose of this review is to integrate data from more than 20 years of heterotransplantation research in the study of small-cell neuroendocrine carcinoma of the prostate (SCNCP). Heterotransplantation has provided data regarding the histopathology, karyotype, DNA content, cell cycle frequency, tumor markers, androgen receptor expression, metastasis and take rate of this prostate disease. When possible, comparisons between original in situ specimens removed from patients and heterotransplanted tissue from host mice have been made. There are advantages, as well as limitations, that have been identified for SCNCP heterotransplants versus xenotransplantation of cultured cells. Overall, heterotransplanted tumors are better than conventional tumor xenografts at retaining tumor morphology, pathology, secretory activity and expression of tumor markers of the patient's original specimen. Furthermore, heterotransplanted tissue preserves the three-dimensional tumor architecture of the prostate to maintain critical stromal-epithelial cell interactions.

Figure 1

Cells of different histologic types compose the prostate gland. Basal cells, luminal cells, small neuroendocrine cells, smooth muscle cells, fibroblasts, vascular cells, nerve cells and basement membrane plus tissue matrix compose the prostate gland. Hormones like testosterone utilize endocrine pathways to affect the prostate microenvironment. Androgen-mediated events use either autocrine signaling pathways, in which the cell secretes peptide growth factors to influence its own growth (e.g., luminal cells to luminal cells), or paracrine pathways, in which the cell elaborates peptide growth factors to affect neighboring cells of a different histologic type. (Reproduced from Prostatic Diseases with permission).