Metastatic breast cancer cells suppress osteoblast adhesion and differentiation
Metastatic breast cancer cells suppress osteoblast adhesion and differentiation
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DOI：
10.1007/s10585-004-1867-6
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发表时间：
2004-01-01
影响因子：
4
通讯作者：
Mastro, AM
中科院分区：
文献类型：
--
作者：
Mercer, RR;Miyasaka, C;Mastro, AM
骨是转移性乳腺癌细胞定植的主要靶点。一旦出现。乳腺癌细胞激活破骨细胞，从而刺激骨质流失。骨骼退化伴随着疼痛和骨折易感性的增加。然而，靶向抑制破骨细胞并不能完全阻止病变的进展，也不能治愈病变。这表明乳腺癌细胞也可能影响成骨细胞，即形成骨骼的细胞。这项研究的重点是确定乳腺癌细胞改变成骨细胞功能的能力。用MDA-MB-231乳腺癌细胞的条件培养液培养MCM-E1成骨细胞，并随后检测分化的变化。通过骨钙素、骨涎蛋白和碱性磷酸酶的表达以及矿化来监测成骨细胞的分化。在MDA-MB-231条件培养液中培养的成骨细胞不表达这些成熟的骨蛋白，也不能矿化基质。成骨细胞分化的抑制可能是由于转化生长因子β存在于MDA-MB-231条件培养液中。有趣的是，乳腺癌条件培养液也改变了细胞黏附。当用干涉反射显微镜和扫描声学显微镜检测成骨细胞的黏附特性时，局灶性黏附斑块减少，脱落部位清晰可见。在条件培养液培养的成骨细胞中，F-肌动蛋白被分解和点状分布，而不是在长的应力纤维中组织。综上所述，这些观察结果表明，转移性乳腺癌细胞改变了成骨细胞的黏附，阻止了分化。这些影响可能解释了骨转移乳腺癌患者在破骨细胞抑制后持续骨质丢失的原因。
Bone is a primary target for colonization of metastatic breast cancer cells. Once present. the breast cancer cell, activate osteoclasts, thereby stimulating bone loss. Bone degradation is accompanied by pain and increased susceptibility to fractures. However, targeted inhibition of osteoclasts does not completely prevent lesion progression, nor does it heal the lesions. This suggests that breast cancer cells may also affect osteoblasts, cells that build bone. The focus of this study was to determine the ability of breast cancer cells to alter osteoblast function. MCM-E1 osteoblasts were cultured with conditioned medium from MDA-MB-231 breast cancer cells and subsequently assayed for changes in differentiation. Osteoblast differentiation was monitored by expression of osteocalcin, bone sialoprotein and alkaline phosphatase, and by mineralization. Osteoblasts cultured with MDA-MB-231 conditioned medium did not express these mature bone proteins, nor did they mineralize a matrix. Inhibition of osteoblast differentiation was found to be due to transforming growth factor beta present in MDA-MB-231 conditioned medium. Interestingly, breast cancer conditioned medium also altered cell adhesion. When osteoblasts were assayed for adhesion properties using interference reflection microscopy and scanning acoustic microscopy, there was a reduction in focal adhesion plaques and sites of detachment were clearly visible. F-actin was disassembled and punctate in osteoblasts cultured with conditioned medium rather than organized in long stress fibers. Taken together, these observations suggest that metastatic breast cancer cells alter osteoblast adhesion and prevent differentiation. These affects could account for the continued loss of bone after osteoclast inhibition in patients with bone-metastatic breast cancer.