Waltregny D, Bellahcène A, de Leval X, Florkin B, Weidle U, Castronovo V
Metastasis Research Laboratory, University of Liège, Belgium.
J Bone Miner Res. 2000 May;15(5):834-43. doi: 10.1359/jbmr.2000.15.5.834.
The recent demonstration that bone sialoprotein (BSP) is expressed in osteotropic cancers suggests that this bone matrix protein might be implicated in the preferential seed and growth of metastatic cells in bone. High expression of BSP in breast and prostate primary carcinomas is associated with progression and bone metastases development. The exact mechanisms by which BSP may favor bone metastases formation are not clearly established yet. Although BSP expression has been detected in breast, prostate, lung, thyroid, and neuroblastoma primary tumors, no information regarding its expression in metastases is available to date. In this study, we have examined BSP expression in 15 bone and 39 visceral metastatic lesions harvested from 8 breast cancer patients and 7 prostate cancer patients who died of disseminated disease. We were able to retrieve the primary lesions from 5 of the 8 breast cancer patients as well as from all 7 prostate cancer patients. All the primary breast tumor patients and 5 of the 7 primary prostate cancer patients expressed a detectable level of BSP. Bone metastases from all 8 breast cancer patients and from 5 out of 7 prostate cancer patients exhibited detectable levels of the protein. Metastatic cells in close contact with bone trabeculae usually were highly positive for BSP. BSP also was detected in secondary lesions developed at visceral sites including liver, thyroid, lung, and adrenal glands. However, BSP expression was significantly lower in visceral metastases than in skeletal ones (Mann-Whitney test, p < 0.05). Our data represent the first demonstration of an increased expression of BSP in bone metastases compared with nonskeletal metastases in human breast and prostate cancers and add weight to the body of evidence attributing a significant role to this protein in the genesis of bone metastases.
近期研究表明,骨唾液蛋白(BSP)在亲骨性癌中表达,提示这种骨基质蛋白可能与转移性细胞在骨中的优先着床和生长有关。BSP在乳腺癌和前列腺癌原发肿瘤中的高表达与疾病进展及骨转移的发生相关。BSP促进骨转移形成的确切机制尚未明确。尽管在乳腺癌、前列腺癌、肺癌、甲状腺癌和神经母细胞瘤原发肿瘤中已检测到BSP表达,但目前尚无关于其在转移灶中表达情况的信息。在本研究中,我们检测了从8例死于播散性疾病的乳腺癌患者和7例前列腺癌患者身上获取的15个骨转移灶和39个内脏转移灶中的BSP表达。我们能够从8例乳腺癌患者中的5例以及所有7例前列腺癌患者中获取原发灶。所有原发性乳腺癌患者以及7例原发性前列腺癌患者中的5例均表达可检测水平的BSP。8例乳腺癌患者的所有骨转移灶以及7例前列腺癌患者中的5例的骨转移灶均检测到该蛋白的可检测水平。与骨小梁紧密接触的转移细胞通常BSP呈高度阳性。在内脏部位如肝脏、甲状腺、肺和肾上腺形成的继发性病灶中也检测到了BSP。然而,内脏转移灶中BSP的表达明显低于骨转移灶(Mann-Whitney检验,p < 0.05)。我们的数据首次证明,与人类乳腺癌和前列腺癌的非骨骼转移相比,骨转移灶中BSP表达增加,这进一步证明了该蛋白在骨转移发生过程中起重要作用。