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Expression of adrenomedullin and peptide amidation activity in human prostate cancer and in human prostate cancer cell lines
- Source :
- Cancer Research, Cancer Research, American Association for Cancer Research, 2001, pp.1196-206, HAL, Scopus-Elsevier, Cancer Research, 2001, pp.1196-206
- Publication Year :
- 2001
- Publisher :
- HAL CCSD, 2001.
-
Abstract
- International audience; After therapeutic hormone deprivation, prostate cancer (CaP) cells often develop androgen-independent growth through not-well-defined mechanisms. The presence of neuroendocrine (NE) cells is often greater in prostate carcinoma than in normal prostate, and the frequency of NE cells correlates with tumor malignancy, loss of androgen sensitivity, increase of autocrine-paracrine activity, and poor prognosis. In some CaPs, neuropeptides have been previously implicated as growth factors. Peptidylglycine alpha-amidating monooxygenase (PAM) is the enzyme producing alpha-amidated bioactive peptides from their inactive glycine-extended precursors. In the present work, we demonstrate that androgen-independent PC-3 and DU145 cell lines, derived from human CaP, express PAM in vitro and in xenografts implanted in athymic nude mice, indicating that they are able to produce alpha-amidated peptides. Contrarily, barely detectable levels of PAM were found in the androgen-sensitive LNCaP cell line. We also show that whereas PC-3 and DU145 cells produce and secrete adrenomedullin (AM), a multifunctional amidated peptide, no expression was found in LNCaP cells. We further demonstrate that AM acts as a growth factor for DU145 cells, which suggests the existence of an autocrine loop mechanism that could potentially drive neoplastic growth. PAM mRNA levels were found to be 3-fold higher in prostate adenocarcinomas compared with that of human benign prostate hyperplasia (BPH) as demonstrated by real-time quantitative reverse transcription-PCR. The analysis of AM message expression in BPH and CaP (Gleason's score, 6-9) shows a clear distinction between benign and CaP. The expression was detected only in adenocarcinomas tissues with a marked increase in samples with a high Gleason's score. Immunocytochemically, AM was localized in the carcinomatous epithelial compartment. NE phenotype, assessed after the immunocytochemical localization of neuron-specific enolase (NSE), was found in both the epithelial and the stromal compartments of cancers; in BPH, only some spare basal cells were NSE-labeled. Cancer progression could be accelerated by peptides secreted by a population of cells capable of inducing androgen-independent tumoral growth via autocrine-paracrine mechanisms.
- Subjects :
- Male
MESH: Neoplasm Proteins
Neoplasms, Hormone-Dependent
Transplantation, Heterologous
Prostatic Hyperplasia
Mice, Nude
[SDV.CAN]Life Sciences [q-bio]/Cancer
Adenocarcinoma
urologic and male genital diseases
MESH: Multienzyme Complexes
MESH: Phosphopyruvate Hydratase
Mixed Function Oxygenases
Adrenomedullin
Mice
MESH: Prostatic Hyperplasia
MESH: In Situ Hybridization
[SDV.CAN] Life Sciences [q-bio]/Cancer
Multienzyme Complexes
MESH: Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
MESH: Mice, Nude
Animals
Humans
MESH: Animals
RNA, Messenger
MESH: Tumor Cells, Cultured
MESH: Neoplasms, Hormone-Dependent
MESH: Transplantation, Heterologous
MESH: Mice
In Situ Hybridization
MESH: RNA, Messenger
MESH: Humans
Reverse Transcriptase Polymerase Chain Reaction
MESH: Peptides
MESH: Adenocarcinoma
Prostatic Neoplasms
MESH: Immunohistochemistry
MESH: Mixed Function Oxygenases
Immunohistochemistry
MESH: Adrenomedullin
MESH: Male
Neoplasm Proteins
Phosphopyruvate Hydratase
MESH: Prostatic Neoplasms
MESH: Cell Division
Peptides
Cell Division
Neoplasm Transplantation
MESH: Neoplasm Transplantation
Subjects
Details
- Language :
- English
- ISSN :
- 00085472 and 15387445
- Database :
- OpenAIRE
- Journal :
- Cancer Research, Cancer Research, American Association for Cancer Research, 2001, pp.1196-206, HAL, Scopus-Elsevier, Cancer Research, 2001, pp.1196-206
- Accession number :
- edsair.pmid.dedup....0414f96707ba0b4ecd436ce25a2b0637