Involvement of heparin affin regulatory peptide in human prostate cancer.
BACKGROUND
Heparin affin regulatory peptide (HARP) composes, together with midkine (MK), a new family of heparin-binding growth/differentiation factors. Recently, HARP was incriminated in cancer progression, as an angiogenic factor and as a tumor growth factor. In this study, we analyzed the possible involvement of HARP in human prostate cancer (Pca).


METHODS
The localization of HARP protein and its mRNAs in normal prostate (n = 5), benign prostate hyperplasia (BPH) (n = 7), and prostate cancer (Pca) (n = 9) was analyzed by immunohistochemistry and in situ hybridization. The mitogenic activity of this growth factor for prostate epithelial cells was determined with a thymidine incorporation assay. HARP cDNA was transfected into normal prostate epithelial (PNT-1A) cells, and their growth was evaluated by soft-agar growth assay.


RESULTS
We found HARP protein associated with epithelial cells in PCa but not in normal prostate or BPH, while the corresponding mRNAs were located in the stromal compartment. Furthermore, HARP is mitogenic for PNT-1A, LNCaP, and DU-145 cells. Overexpression of the human HARP in PNT-1A transfected cells induced both anchorage-independent growth and growth at low serum concentrations.


CONCLUSIONS
Our results suggest that HARP may act in a paracrine manner from mesenchymal to tumoral epithelial cells, and may play a role in the molecular mechanisms that regulate prostate tumor cell growth.
Vacherot
F
F
Laboratoire de Recherche sur la Croissance Cellulaire, la Réparation et la Regénération Tissulaires, Université Paris XII-Val de Marne, Créteil, France.
Caruelle
D
D
Chopin
D
D
Gil-Diez
S
S
Barritault
D
D
Caruelle
J P
JP
Courty
J
J
D016475:3T3 Cells; D000230:Adenocarcinoma / Q000737:chemistry / Q000473:pathology; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D000078792:Midkine; D008934:Mitogens / Q000032:analysis / Q000378:metabolism*; D011467:Prostate / Q000737:chemistry*; D011470:Prostatic Hyperplasia / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D014162:Transfection; D014407:Tumor Cells, Cultured