Instituto Nacional de Câncer, Coordenação de Pesquisa, Programa de Oncobiologia Celular e Molecular, Rio de Janeiro, Brazil.
Instituto Nacional de Câncer, Coordenação de Pesquisa, Programa de Hematologia-Oncologia Pediátrico, Rio de Janeiro, Brazil.
Cancer Lett. 2017 Nov 1;408:138-143. doi: 10.1016/j.canlet.2017.08.022. Epub 2017 Aug 24.
Osteopontin (OPN) is a protein expressed in several tissues, including bone marrow, in which it performs distinct roles, such as modulating hematopoietic stem cell niche and bone remodeling. Most data in hematological malignancies (HMs) refers to total OPN (tOPN), comprehending the sum of distinct OPN splicing isoforms (OPN-SI), while reports describing the expression and roles of each OPN-SI are scarce. This review aims to summarize tOPN roles in HMs and provide evidence that OPN-SIs can also modulate specific functions in HMs biology. We summarize that upregulated tOPN can modulate HMs (leukemia, lymphoma and myeloma) progression, inducing cell adhesion, invasion, angiogenesis, cell differentiation and extramedullary and/or central nervous system infiltration. Based on this expression pattern, tOPN has been pointed out as a biomarker in those HMs, thus providing potential targets for therapeutic approaches. Our group found that OPN-SIs are expressed in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cell lines (unpublished data), providing early evidence that OPN-SIs are also expressed in BCP-ALL. Further studies should investigate whether these OPN-SIs can differently modulate HMs biology and their putative application as auxiliary biomarkers for HMs.
骨桥蛋白（OPN）是一种在多种组织中表达的蛋白质，包括骨髓，在这些组织中，它发挥着不同的作用，如调节造血干细胞龛和骨骼重塑。大多数关于血液恶性肿瘤（HMs）的数据指的是总骨桥蛋白（tOPN），包括不同骨桥蛋白剪接异构体（OPN-SI）的总和，而描述每个 OPN-SI 表达和作用的报告则很少。这篇综述旨在总结 tOPN 在 HMs 中的作用，并提供证据表明 OPN-SIs 也可以调节 HMs 生物学中的特定功能。我们总结得出，上调的 tOPN 可以调节 HMs（白血病、淋巴瘤和骨髓瘤）的进展，诱导细胞黏附、侵袭、血管生成、细胞分化以及骨髓外和/或中枢神经系统浸润。基于这种表达模式，tOPN 已被指出是这些 HMs 的生物标志物，从而为治疗方法提供了潜在的靶点。我们的研究小组发现，OPN-SIs 在儿童 B 细胞前体急性淋巴细胞白血病（BCP-ALL）细胞系中表达（未发表的数据），这为 OPN-SIs 也在 BCP-ALL 中表达提供了早期证据。进一步的研究应探讨这些 OPN-SIs 是否可以不同地调节 HMs 生物学及其作为 HMs 辅助生物标志物的潜在应用。
