Rat prostate adenocarcinoma cells disseminate to bone and adhere preferentially to bone marrow-derived endothelial cells.

Rat prostate adenocarcinoma cells disseminate to bone and adhere preferentially to bone marrow-derived endothelial cells.
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发表时间:
1992-09
期刊:
影响因子:
11.2
通讯作者:
M. Haq;D. Goltzman;G. Tremblay;P. Brodt
M. Haq;D. Goltzman;G. Tremblay;P. Brodt
中科院分区:
医学1区
文献类型:
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作者:
M. Haq;D. Goltzman;G. Tremblay;P. Brodt

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大约70%的前列腺癌患者会发生骨转移。转移性前列腺癌与高死亡率相关,是男性癌症相关死亡的主要原因。为了研究前列腺癌细胞对骨骼的偏爱背后的宿主-肿瘤相互作用,我们用大鼠邓宁癌Mat-LyLu细胞建立了实验模型。将这些细胞接种到心脏左心室导致100%的接种动物发生脊髓转移。Mat-LyLu亚系(Mat-LyLu- b5)随后通过连续接种骨髓来源的癌细胞进入左心室,发现与亲本系相比具有更高的转移潜力。然后利用转移系和原代培养的大鼠骨髓源性基质细胞,在体外研究肿瘤细胞粘附宿主细胞在骨髓定植过程中的可能作用。研究发现,转移的Mat-LyLu细胞与内皮细胞高度富集的骨髓基质细胞培养物的粘附性显著高于与其他骨源性细胞的粘附性,包括非内皮骨髓基质细胞(3.5倍)和成骨细胞(1.7倍)。与大鼠成纤维细胞(7x)和肝内皮细胞(7.5x)相比,其黏附率也显著提高。提示前列腺癌细胞与骨髓内皮的粘附可能在其骨转移过程中起一定作用。
Approximately 70% of patients with prostatic cancer develop bone metastases. Metastatic prostate adenocarcinomas are associated with high mortality rates and represent a leading cause of cancer-related deaths among males. To study the host-tumor interactions underlying the predilection of prostate cancer cells for skeletal bone, an experimental model was developed using rat Dunning carcinoma Mat-LyLu cells. Inoculations of these cells into the left ventricle of the heart led to the development of spinal metastases in 100% of inoculated animals. A subline of Mat-LyLu (Mat-LyLu-B5) was subsequently selected through the sequential inoculation of bone marrow-derived carcinoma cells into the left ventricle and was found to have an increased metastatic potential compared to the parental line. The possible role of tumor cell adhesion to host cells in the process of bone marrow colonization was then investigated in vitro using the metastatic line and primary cultures of rat bone marrow-derived stromal cells. It was found that the adhesion of the metastatic Mat-LyLu cells to a bone marrow stromal cell culture highly enriched for endothelial cells was significantly higher than the adhesion to other bone-derived cells, including nonendothelial bone marrow stromal cells (3.5x) and osteoblasts (1.7x). It was also significantly higher than the adhesion to rat fibroblasts (7x) and to hepatic endothelial cells (7.5x). The results suggest that the adhesion of prostate carcinoma cells to the bone marrow endothelium may play a role in their metastasis to bone.