Clinical and experimental progression of a new model of human prostate cancer and therapeutic approach

Citation
G. De Pinieux et al., Clinical and experimental progression of a new model of human prostate cancer and therapeutic approach, AM J PATH, 159(2), 2001, pp. 753-764
Citations number
51
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Journal title
AMERICAN JOURNAL OF PATHOLOGY
ISSN journal
00029440 → ACNP
Volume
159
Issue
2
Year of publication
2001
Pages
753 - 764
Database
ISI
SICI code
0002-9440(200108)159:2<753:CAEPOA>2.0.ZU;2-A
Abstract
We report the clinical evolution of a prostate cancer, metastasizing to lun gs and bones, recurring locally, and escaping from anti-androgen therapy. K ey event of biological progression of the patient's tumor was the coinciden ce of allelic imbalance accumulation and of bone metastases occurrence. The recurrent tumor was established as the transplantable xenograft PAC120 in nude mice, where it grew locally. PAC120 displayed the same immunophenotype of the original tumor (positive for keratin, vimentin, prostatic acid phos phatase, and Leu-7) and expressed human HOXB9, HOXA4, HER-2/neu, and prosta te-specific antigen genes, as detected by reverse transcriptase-polymerase chain reaction. it formed lung micrometastases detected by mRNA expression of human genes. Cytogenetic analysis demonstrated numerous alterations refl ecting the tumor evolution. PAC120 was still hormone-dependent; its growth was strongly inhibited by the new gonadotropin-releasing hormone antagonist FE 200486 but weakly by gonadotropin-releasing hormone superagonist D-Trp( 6)-luteinizing-hormone releasing hormone (decapeptyl). Tumor growth inhibit ion induced by anti-hormone therapy was linked to the hormone deprivation d egree, more important and more stable with FE 200486 than with D-Trp(6)-lut einizing-hormone releasing hormone. Surgical castration of mice led to tumo r regressions but did not prevent late recurrences. Transition to hormone-i ndependent tumors was frequently associated with a mucoid differentiation o r with a neuroendocrine-like pattern. independent variations of mRNA expres sion of HER-2/neu and prostate-specific antigen were observed in hormone-in dependent tumors whereas HOX69 gene expression was constant. In conclusion, PAC120 xenograft, a new model of hormone-dependent prostate cancer retaine d the progression potential of the original tumor, opening the opportunity to study the hormone dependence escape mechanism.