SPP1 Derived from Macrophages Is Associated with a Worse Clinical Course and Chemo-Resistance in Lung Adenocarcinoma.
SPP1 Derived from Macrophages Is Associated with a Worse Clinical Course and Chemo-Resistance in Lung Adenocarcinoma.
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骨桥蛋白，也称为分泌型磷蛋白1（SPP 1），由癌细胞表达，被认为是一种不良预后因子。尽管肿瘤相关巨噬细胞（tumor-associated macrophages，TAMs）产生SPP 1的研究近年来备受关注，但尚未有区分肿瘤细胞和TAMs SPP 1表达的研究。在本研究中，我们证明了以下几点。(1)TAM上SPP 1表达增加与EGFR野生型腺癌的临床病程恶化相关。(2)巨噬细胞上SPP 1的表达依赖于GM-CSF介导的巨噬细胞分化。(3)巨噬细胞来源的SPP 1可能有助于肺癌的化疗耐药性。骨桥蛋白（Osteopontin），又称分泌型磷蛋白1（SPP 1），是一种多功能的分泌型磷酸化糖蛋白。SPP 1也在肿瘤细胞中表达，许多研究表明，高水平的循环SPP 1与各种癌症的不良预后相关。SPP 1不仅由肿瘤细胞表达，而且由基质细胞如巨噬细胞表达。然而，还没有研究区分癌细胞和肿瘤相关巨噬细胞（TAM）的SPP 1表达。因此，在本研究中，我们试图通过使用双重免疫组织化学来准确地评估SPP 1在非小细胞肺癌患者的癌细胞和TAM上的表达状态。我们证明，在肺腺癌患者中，TAM上SPP 1的高表达预示着不良预后。此外，我们使用人单核细胞衍生的巨噬细胞研究了与SPP 1相关的表达机制，并揭示了SPP 1表达水平在粒细胞-巨噬细胞集落刺激因子介导的巨噬细胞分化中增加。此外，SPP 1有助于肺癌细胞系中的抗癌药物耐药性。结论：肺腺癌患者TAM表面SPP 1的表达与肿瘤细胞的耐药性有关，提示TAM表面SPP 1的表达与肿瘤细胞的耐药性有关。
Osteopontin, also called secreted phosphoprotein 1 (SPP1), is expressed by cancer cells and is known as a poor prognostic factor. Although the production of SPP1 by tumor-associated macrophages (TAMs) has been attracting much attention recently, there have been no studies distinguishing the SPP1 expression of cancer cells and TAMs. In the present study, we demonstrated the following points. (1) Increased SPP1 expression on TAMs is associated with a worse clinical course in EGFR-wild-type adenocarcinoma. (2) SPP1 expression on macrophages is dependent on GM-CSF-mediated macrophage differentiation. (3) Macrophage-derived SPP1 potentially contributed to chemoresistance in lung cancer. Osteopontin, also called secreted phosphoprotein 1 (SPP1), is a multifunctional secreted phosphorylated glycoprotein. SPP1 is also expressed in tumor cells, and many studies demonstrated that a high level of circulating SPP1 is correlated with a poor prognosis in various cancers. SPP1 is expressed not only by tumor cells but also by stromal cells, such as macrophages. However, there have been no studies distinguishing the SPP1 expression of cancer cells and tumor-associated macrophages (TAMs). Thus, in this study, we tried to accurately evaluate the SPP1 expression status on cancer cells and TAMs separately in patients with non-small cell lung cancer by using double immunohistochemistry. We demonstrated that high SPP1 expression on TAMs predicted a poor prognosis in lung adenocarcinoma patients. Additionally, we investigated the expression mechanisms related to SPP1 using human-monocyte-derived macrophages and revealed that the SPP1 expression level increased in macrophage differentiation mediated by granulocyte-macrophage colony-stimulating factor. Furthermore, SPP1 contributed to anti-cancer drug resistance in lung cancer cell lines. In conclusion, SPP1 production on TAMs predicted a poor prognosis in lung adenocarcinoma patients, and TAM-derived SPP1′s involvement in the chemo-resistance of cancer cells was suggested.
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