Serum osteopontin, an enhancer of tumor metastasis to bone, promotes B16 melanoma cell migration
Serum osteopontin, an enhancer of tumor metastasis to bone, promotes B16 melanoma cell migration
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DOI：
10.1002/jcb.21298
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发表时间：
2007-07-01
影响因子：
4
通讯作者：
Noda, Masaki
中科院分区：
文献类型：
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作者：
Hayashi, Chikako;Rittling, Susan;Noda, Masaki
肿瘤的恶性程度与其增殖能力和转移频率等特征有关。由于肿瘤转移缩短了患者的生命，因此建立抗转移的治疗方法非常重要。骨桥蛋白（Osteopontin，OPN）在骨基质中大量表达，通过与其受体α v β 3整合素相互作用，参与细胞粘附、迁移、细胞外基质（extracellular matrix，ECM）侵袭和细胞增殖。骨桥蛋白被认为是体内肿瘤转移的正性调节因子。然而，OPN如何调节转移在很大程度上是未知的。在这里，我们探讨OPN在细胞迁移中的作用。来自野生型小鼠的血清诱导B16黑色素瘤细胞的细胞迁移，而来自OPN缺陷型小鼠的血清抑制该事件。与含白蛋白的培养基相比，重组OPN的存在显著增强细胞迁移。OPN诱导的细胞迁移通过抑制ERK/MAPK通路而被抑制，表明OPN诱导的细胞迁移依赖于该通路。OPN在这些癌细胞中的过表达本身促进细胞增殖并倾向于增加B16细胞迁移，这表明OPN通过在宿主微环境和肿瘤细胞本身中发挥双重作用来促进骨转移。总之，OPN在宿主组织和肿瘤细胞中的表达升高促进了肿瘤细胞向肿瘤转移的迁移阅读，表明中和OPN诱导的信号可能有效地抑制肿瘤转移。
Tumor malignancy is associated with several features Such as proliferation ability and frequency of metastasis. Since tumor metastasis shortens patients' lifetime, establishment of therapy for anti-metastasis is very important. Osteopontin (OPN), which abundantly expressed in bone matrix, is involved in cell adhesion, migration, extracellular matrix (ECM) invasion and cell proliferation via interaction with its receptor, that is, alpha v beta 3 integrin. OPN is believed to be a positive regulator of tumor metastasis in vivo. However, how OPN regulates metastasis is largely unknown. Here, we explore the role of OPN in cell migration. Serum from wild-type mice induced cell migration of B16 melanoma cells, while serum from OPN-deficient mouse suppressed this event. The presence of recombinant OPN significantly enhanced cell migration compared to albumin containing medium. OPN-induced cell migration was suppressed by inhibiting the ERK/MAPK pathway indicating that OPN-induced cell migration depends on this pathway. Overexpression of OPN in these cancer cells per se promoted cell proliferation and tended to increase B16 cell migration suggesting that OPN promotes bone metastasis by playing dual roles both in host microenvironment and in tumor cell itself. In conclusion, the elevated OPN expression in host tissue and tumor cell itself promotes tumor cell migration reading to tumor metastasis, suggesting that neutralization of OPN-induced signal might be effective in suppression of tumor metastasis.