Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
J Mol Med (Berl). 2011 Dec;89(12):1167-74. doi: 10.1007/s00109-011-0792-9. Epub 2011 Aug 13.
Migratory capacity is a fundamental property of hematopoietic stem and progenitor cells (HSPCs). This feature is employed in clinical mobilization of HSPCs to the circulation and constitutes the basis for modern bone marrow (BM) transplantation procedures which are routinely used to treat hematological malignancies. Therefore, characterization of new players in the complex process of HSPC motility in steady-state conditions as well as during stress situations is a major challenge. We report that while the metalloproteinase membrane type 1-metalloprotease (MT1-MMP) has an essential role in human HSPC trafficking during granulocyte colony-stimulating factor (G-CSF)-induced mobilization, its inhibitor reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and the adhesion molecule CD44 are required for HSPC retention to the BM in steady-state conditions. The nervous system via Wnt signaling along with HGF/c-Met signaling and the complement cascade play a major role in regulating MT1-MMP increased activity, CD44 cleavage, and RECK-reduced expression during G-CSF-induced mobilization. This review will elaborate on the opposite roles of MT1-MMP and RECK in HSPC migration and retention and suggest targeting them in order to facilitate HSPC mobilization and engraftment upon BM transplantation in patients.
迁移能力是造血干细胞和祖细胞 (HSPCs) 的基本特性。这一特性被用于临床中将 HSPCs 动员到循环中，构成了现代骨髓 (BM) 移植程序的基础，这些程序通常用于治疗血液系统恶性肿瘤。因此，在稳态条件下以及在应激情况下，对 HSPC 迁移过程中新型参与者进行特征描述是一个主要挑战。我们报告称，虽然金属蛋白酶膜型 1-金属蛋白酶 (MT1-MMP) 在粒细胞集落刺激因子 (G-CSF) 诱导的动员过程中对人类 HSPC 迁移具有重要作用，但它的抑制剂逆转诱导富含半胱氨酸的 Kazal 基序的蛋白 (RECK) 和黏附分子 CD44 在稳态条件下对 HSPC 保留在 BM 中是必需的。神经系统通过 Wnt 信号以及 HGF/c-Met 信号和补体级联反应，在调节 G-CSF 诱导的动员过程中 MT1-MMP 活性增加、CD44 裂解和 RECK 表达减少方面发挥着重要作用。这篇综述将详细阐述 MT1-MMP 和 RECK 在 HSPC 迁移和保留中的相反作用，并提出针对它们的治疗方法，以促进患者 BM 移植后 HSPC 的动员和植入。
