Roles of osteonectin in the migration of breast cancer cells into bone.
Roles of osteonectin in the migration of breast cancer cells into bone.
复制标题
骨连接蛋白在乳腺癌细胞迁移到骨中的作用。
DOI：
10.1002/jcb.20644
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Gay,CarolV
中科院分区：
文献类型：
--
作者：
CampoMcKnight,DianaleeA;Sosnoski,DonnaM;Koblinski,JenniferE;Gay,CarolV
这项研究的重点是深入了解骨连蛋白(S)在乳腺癌细胞向骨的优先转移中的作用。从乳腺癌(MDA-MB-435、MDA-MB-468)、成骨细胞(hFOB1.19)、非肿瘤性乳腺上皮细胞(hTERT-HME1)和骨活检分离的血管内皮细胞(HBME-1)的条件培养液中分离到骨连接蛋白。分析这五种来源的骨连蛋白的化学/物理性质，以确定是否存在独特的骨连蛋白构型，从而鉴定趋化异构体。所有来源的骨连素的分子质量均为∼46 kDa，N-连接的糖基化，以及检测不到的磷酸化丝氨酸、唾液酸和O-连接的寡糖。乳腺癌、成骨细胞和乳腺上皮细胞系中的骨结素的cDNA值是相同的，而血管内皮细胞的cDNA点突变导致8个氨基酸替换。然后分析骨源性骨连蛋白，以评估其对乳腺癌细胞运动和迁移的影响。尽管骨连蛋白增加了非定向的MDA-MB-231细胞的运动能力，但它并不能吸引相同的乳腺癌细胞株。然而，乳腺癌细胞确实迁移到了已知的化学诱导剂Vitronectin，以及来自野生型和骨连接素缺失小鼠的骨提取液。当骨连接蛋白也存在时，向玻璃体连接蛋白的迁移被促进。我们得出结论，骨连蛋白不是一种趋化因子。然而，通过其抗黏附特性，骨连接蛋白诱导了乳腺癌细胞的非定向运动，并可能增强了对玻璃体连接蛋白的化学吸引力。J.细胞。生物化学。©2005 Wiley-Liss Inc.
The focus of this study was to gain insight into the role(s) of osteonectin in the preferential metastasis of breast cancer cells to bone. Osteonectin was isolated from conditioned media of several cell lines including breast cancer (MDA‐MB‐435, MDA‐MB‐468), osteoblasts (hFOB1.19), non‐neoplastic breast epithelial (hTERT‐HME1), and vascular endothelial cells isolated from a bone biopsy (HBME‐1). Chemical/physical properties of osteonectin from these five sources was analyzed to determine if unique configurations of osteonectin exist and therefore identify a chemotactic isoform. Osteonectin from all sources had a molecular weight of ∼46 kDa, N‐linked glycosylation, and undetectable phosphorylated serines, sialic acids and O‐linked oligosaccharides. The cDNA for osteonectin from the breast cancer, osteoblast, and breast epithelial cell lines was identical, while the vascular endothelial cell cDNA contained point mutations that resulted in eight amino acid substitutions. Bone‐derived osteonectin was then analyzed to assess its influence on breast cancer cell motility and migration. Although osteonectin increased undirected MDA‐MB‐231 cell motility, it did not chemoattract the same breast cancer cell line. However, the breast cancer cells did migrate toward the known chemoattractant vitronectin and to bone extracts derived from wild‐type and osteonectin‐null mice. Migration to vitronectin was enhanced when osteonectin was also present. We concluded that osteonectin was not a chemotactic factor. However, through its anti‐adhesive properties, osteonectin induced undirected breast cancer cell motility, and may have enhanced chemoattraction to vitronectin. J. Cell. Biochem. © 2005 Wiley‐Liss, Inc.