Ribatti Domenico, Moschetta Michele, Vacca Angelo
Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy, National Cancer Institute "Giovanni Paolo II", Bari, Italy.
Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy.
Thromb Res. 2014 May;133 Suppl 2:S102-6. doi: 10.1016/S0049-3848(14)50017-5.
In patients with multiple myeloma (MM), the bone marrow (BM) contains hematopoietic stem cells (HSCs) and non-hematopoietic cells. HSCs are able to give rise to all types of mature blood cells, while the non hematopoietic component includes mesenchymal stem cells (MSCs), fibroblasts, osteoblasts, osteoclasts, chondroclasts, endothelial cells, endothelial progenitor cells (EPCs), B and T lymphocytes, NK cells, erythrocytes, megakaryocytes, platelets, macrophages and mast cells. All of these cells form specialized "niches" in the BM microenvironment which are close to the vasculature ("vascular niche") or to the endosteum ("osteoblast niche"). The "vascular niche" is rich in blood vessels where endothelial cells and mural cells (pericytes and smooth muscle cells) create a microenvironment that affects the behavior of several stem and progenitor cells. The vessel wall serves as an independent niche for the recruitment of endothelial progenitor cells, MSCs and HSCs. The activation by angiogenic factors and inflammatory cytokines switch the "vascular niche" to promote MM tumor growth and spread. This review will focus on the mechanisms involved in the generation of signals released by endothelial cells in the "vascular niche" that promote tumor growth and spread in MM.
在多发性骨髓瘤（MM）患者中，骨髓（BM）包含造血干细胞（HSCs）和非造血细胞。造血干细胞能够产生所有类型的成熟血细胞，而非造血成分包括间充质干细胞（MSCs）、成纤维细胞、成骨细胞、破骨细胞、软骨破骨细胞、内皮细胞、内皮祖细胞（EPCs）、B和T淋巴细胞、自然杀伤细胞（NK细胞）、红细胞、巨核细胞、血小板、巨噬细胞和肥大细胞。所有这些细胞在骨髓微环境中形成特殊的“龛位”，这些龛位靠近脉管系统（“血管龛位”）或骨内膜（“成骨细胞龛位”）。“血管龛位”富含血管，内皮细胞和壁细胞（周细胞和平滑肌细胞）在其中创造了一个影响多种干细胞和祖细胞行为的微环境。血管壁作为募集内皮祖细胞、间充质干细胞和造血干细胞的独立龛位。血管生成因子和炎性细胞因子的激活会使“血管龛位”转变，从而促进MM肿瘤的生长和扩散。本综述将聚焦于“血管龛位”中内皮细胞释放的促进MM肿瘤生长和扩散的信号产生机制。
