Vacherot F, Caruelle D, Chopin D, Gil-Diez S, Barritault D, Caruelle J P, Courty J
Laboratoire de Recherche sur la Croissance Cellulaire, la Réparation et la Regénération Tissulaires, Université Paris XII-Val de Marne, Créteil, France.
Prostate. 1999 Feb 1;38(2):126-36. doi: 10.1002/(sici)1097-0045(19990201)38:2<126::aid-pros6>3.0.co;2-c.
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).
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.
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.
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.
肝素亲和调节肽（HARP）与中期因子（MK）共同构成了一个新的肝素结合生长/分化因子家族。最近，HARP被认为与癌症进展有关，是一种血管生成因子和肿瘤生长因子。在本研究中，我们分析了HARP在人类前列腺癌（Pca）中的可能作用。
通过免疫组织化学和原位杂交分析HARP蛋白及其mRNA在正常前列腺（n = 5）、良性前列腺增生（BPH）（n = 7）和前列腺癌（Pca）（n = 9）中的定位。用胸苷掺入试验测定该生长因子对前列腺上皮细胞的促有丝分裂活性。将HARP cDNA转染到正常前列腺上皮（PNT-1A）细胞中，通过软琼脂生长试验评估其生长情况。
我们发现HARP蛋白在前列腺癌的上皮细胞中表达，而在正常前列腺或良性前列腺增生中不表达，而相应的mRNA位于间质区。此外，HARP对PNT-1A、LNCaP和DU-145细胞具有促有丝分裂作用。在转染的PNT-1A细胞中过表达人HARP可诱导非锚定依赖性生长和低血清浓度下的生长。
我们的结果表明，HARP可能以旁分泌方式从间充质细胞作用于肿瘤上皮细胞，并可能在调节前列腺肿瘤细胞生长的分子机制中发挥作用。
