Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Histopathology. 2012 Feb;60(3):443-51. doi: 10.1111/j.1365-2559.2011.04112.x.
Interaction with the bone marrow microenvironment is important for homing and survival of myeloma cells. One cytokine involved in this process is hepatocyte growth factor (HGF). HGF, by binding to the receptor tyrosine kinase c-Met, mediates a broad range of tumour progression activities. Our aims were to investigate whether HGF and c-Met are present in bone marrow and extramedullary tumours from patients with monoclonal plasma cell disease, and whether c-Met is activated.
Expression of HGF, c-Met and phospho-c-Met was studied by immunohistochemistry in biopsies from 80 patients with monoclonal plasma cell disease. Cytoplasmic staining for HGF in plasma cells was demonstrated in 58 of 68 biopsies from multiple myeloma patients (85%), but also in biopsies from nine of 10 healthy individuals. Membranous staining for c-Met was found in 25 of 63 multiple myeloma patients (40%) and in none of 10 healthy individuals. Membranous staining for phospho-c-Met was found in biopsies from 15 of 21 c-Met-positive myeloma patients (71%).
Our data point to c-Met expression as one of the factors that distinguishes normal from malignant plasma cells, and indicate that the HGF/c-Met system is activated in multiple myeloma patients.
骨髓微环境的相互作用对骨髓瘤细胞的归巢和存活很重要。参与这一过程的一种细胞因子是肝细胞生长因子（HGF）。HGF 通过与受体酪氨酸激酶 c-Met 结合，介导广泛的肿瘤进展活性。我们的目的是研究单克隆浆细胞疾病患者的骨髓和骨髓外肿瘤中是否存在 HGF 和 c-Met，以及 c-Met 是否被激活。
对 80 例单克隆浆细胞疾病患者的活检标本进行免疫组织化学研究，以研究 HGF、c-Met 和磷酸化 c-Met 的表达。68 例多发性骨髓瘤患者的 58 例活检标本中（85%）显示浆细胞的 HGF 细胞质染色，但 10 例健康个体的 9 例活检标本中也显示 HGF 细胞质染色。25 例多发性骨髓瘤患者（40%）的 63 例活检标本中存在 c-Met 的膜染色，而 10 例健康个体的活检标本中均未发现 c-Met 的膜染色。在 21 例 c-Met 阳性的骨髓瘤患者的 15 例活检标本中发现了磷酸化 c-Met 的膜染色。
我们的数据表明 c-Met 表达是区分正常和恶性浆细胞的因素之一，并表明 HGF/c-Met 系统在多发性骨髓瘤患者中被激活。
