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小鼠骨肉瘤细胞中血管内皮生长因子(VEGF)和骨形态发生蛋白(BMP)的表达

VEGF and BMP expression in mouse osteosarcoma cells.

作者信息

Weiss Kurt R, Cooper Gregory M, Jadlowiec Julie A, McGough Richard L, Huard Johnny

机构信息

Stem Cell Research Center, Children's Hospital of Pittsburgh and Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.

出版信息

Clin Orthop Relat Res. 2006 Sep;450:111-7. doi: 10.1097/01.blo.0000229333.98781.56.

Abstract

Osteosarcoma is the most common primary bone malignancy. Despite improvements in therapy, approximately 30% of patients experience pulmonary metastasis. Expression of several growth factors, including VEGF and BMPs, has been implicated in tumor progression and metastatic potential. We hypothesized increased metastatic potential of mouse osteosarcoma cells positively correlates with the expression of VEGF and BMPs. We studied the expression patterns of these growth factors in two murine osteosarcoma cell lines with varying degrees of metastatic potential: K7M2 (highly metastatic) and K12 (minimally metastatic). Expression of VEGF and BMP2 were higher in the metastatic K7M2 cell line. We also investigated the effects of the BMP antagonist noggin on osteosarcoma growth characteristics in vitro. We noted decreased motility, altered morphology, and increased cell death in the highly metastatic K7M2 cell line. Less metastatic K12 cells showed substantial cell death without clear alteration of motility or morphology. These data suggest BMP2 expression may be an important factor in osteosarcoma metastasis and noggin administration theoretically could block its actions. Inhibition of BMPs and VEGF should be investigated further as a possible strategy for decreasing the incidence of pulmonary metastases in osteosarcoma.

摘要

骨肉瘤是最常见的原发性骨恶性肿瘤。尽管治疗方法有所改进,但仍有大约30%的患者会发生肺转移。包括血管内皮生长因子(VEGF)和骨形态发生蛋白(BMPs)在内的几种生长因子的表达与肿瘤进展和转移潜能有关。我们推测小鼠骨肉瘤细胞转移潜能的增加与VEGF和BMPs的表达呈正相关。我们研究了这两种具有不同转移潜能的小鼠骨肉瘤细胞系:K7M2(高转移性)和K12(低转移性)中这些生长因子的表达模式。VEGF和BMP2在高转移性的K7M2细胞系中的表达更高。我们还研究了BMP拮抗剂头蛋白(noggin)对骨肉瘤体外生长特性的影响。我们注意到高转移性的K7M2细胞系的运动性降低、形态改变以及细胞死亡增加。低转移性的K12细胞显示出大量细胞死亡,但运动性或形态没有明显改变。这些数据表明BMP2的表达可能是骨肉瘤转移的一个重要因素,理论上给予头蛋白可能会阻断其作用。作为降低骨肉瘤肺转移发生率的一种可能策略,对BMPs和VEGF的抑制应进一步研究。

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