Stromal factors involved in prostate carcinoma metastasis to bone
Stromal factors involved in prostate carcinoma metastasis to bone
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DOI：
10.1002/cncr.11181
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发表时间：
2003-02-01
期刊：
影响因子：
6.2
通讯作者：
Pienta, KJ
中科院分区：
文献类型：
--
作者：
Cooper, CR;Chay, CH;Pienta, KJ
背景前列腺癌（PC）经常转移到骨，在那里它会导致显著的发病率和死亡率。原发和转移靶器官中的基质成分是肿瘤细胞内渗、化学吸引、与靶器官微血管内皮粘附、外渗和转移部位生长的重要介质。基质因子在骨转移中的作用是通过比较骨源性细胞PC细胞系与软组织源性细胞PC细胞系的环状DNA微阵列，并通过评价所选基质成分对PC细胞趋化性、细胞粘附于人骨髓内皮（HBME）和PC细胞生长的影响来确定的。作者证明，PC细胞表达蛋白酶激活受体1（PARI;凝血酶受体），与正常前列腺组织相比，其表达在PC中上调。此外，与软组织PC细胞系（DUCaP、DU 145和LNCaP）相比，骨源性PC细胞系（VCaP和PC-3）中的这种过表达非常明显。作者报告说，骨基质因子，包括基质细胞衍生因子I（SDF-1）和I型胶原肽，是PC细胞的化学引诱物，并且他们证明这些因子中的一些（例如，细胞外基质成分、转化生长因子0、骨形态发生蛋白[BMP]和SDF-1）显著改变体外PC-HBME相互作用。最后，基质因子，如BMP，可以调节PC细胞的体外增殖。间质的可溶性和不溶性成分参与PC向骨转移的多个步骤。作者推测PARI可能在前列腺肿瘤发生中起重要作用。(C)2003年美国癌症协会。
BACKGROUND. Prostate carcinoma (PC) frequently metastasizes to bone, where it causes significant morbidity and mortality. Stromal elements in the primary and metastatic target organs are important mediators of tumor cell intravasation, chemoattraction, adhesion to target organ microvascular endothelium, extravasation, and growth at the metastatic site.METHODS. The role of stromal factors in bone metastasis was determined with a cyclic DNA microarray comparison of a bone-derived cell PC cell line with a soft tissue-derived cell PC cell line and by evaluating the effects of selected stromal components on PC cell chemotaxis, cell adhesion to human bone marrow endothelium (HBME), and PC cell growth.RESULTS. The authors demonstrate that PC cells express protease-activated receptor 1 (PARI; thrombin receptor), and its expression is up-regulated in PC compared with normal prostate tissue. In addition, this overexpression was very pronounced in bone-derived PC cell lines (VCaP and PC-3) compared with soft tissue PC cell lines (DUCaP, DU145, and LNCaP). The authors report that bone stromal factors, including stromal cell-derived factor I (SDF-1) and collagen Type I peptides, are chemoattractants for PC cells, and they demonstrate that some of these factors (e.g., extracellular matrix components, transforming growth factor 0, bone morphogenic proteins [BMPs], and SDF-1) significantly alter PC-HBME interaction in vitro. Finally, stromal factors, such as BMPs, can regulate the proliferation of PC cells in vitro.CONCLUSIONS. Soluble and insoluble elements of the stroma are involved in multiple steps of PC metastasis to bone. The authors hypothesize that PARI may play a central role in prostate tumorigenesis. (C) 2003 American Cancer Society.