Barton B E, Murphy T F
Department of Surgery, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, 185 S. Orange Avenue, Newark, New Jersey 07103, USA.
Cytokine. 2000 Oct;12(10):1537-45. doi: 10.1006/cyto.2000.0748.
Myeloma is a neoplasm thought to "home" to bone marrow. However, evidence for bone-marrow-specific receptors or adhesion molecules expressed on myeloma cells is scanty. Initial myeloma expansion is thought to be due to IL-6 and/or related cytokines. Previous determinations of cytokine expression in bone marrow were performed on bone marrow stromal lines; these findings may not reflect the constitutive pattern of expression in situ. Intracytoplasmic staining for IL-6-like cytokines revealed constitutive expression of some factors in the bone marrow of normal mice, but not spleens. Spleens of myeloma-transplanted SCID mice expressed IL-6-like cytokines, indicative of induction of expression by myeloma. Some cytokines expressed in bone marrow induced myeloma proliferation in the presence of dexamethasone, demonstrating dependence of the myeloma on these cytokines. Our data imply that, rather than "homing" to bone marrow, myeloma cells proliferated within marrow cavities more than in other organs because of growth factors constitutively expressed by bone marrow cells. As myeloma progressed, we observed the induction of growth factor expression in spleen cells. Furthermore, because cytokines other than IL-6 may induce myeloma cell proliferation, therapy aimed at neutralizing IL-6 may not be the most effective method to treat this disease. These findings have implications for both the pathophysiology and therapy of multiple myeloma.
骨髓瘤是一种被认为会“归巢”至骨髓的肿瘤。然而，关于骨髓瘤细胞上表达的骨髓特异性受体或黏附分子的证据却很少。骨髓瘤的初始增殖被认为是由于白细胞介素-6（IL-6）和/或相关细胞因子所致。先前对骨髓中细胞因子表达的测定是在骨髓基质细胞系上进行的；这些发现可能无法反映原位表达的组成模式。对IL-6样细胞因子的胞质内染色显示，正常小鼠的骨髓中某些因子呈组成性表达，但脾脏中则没有。移植了骨髓瘤的严重联合免疫缺陷（SCID）小鼠的脾脏表达IL-6样细胞因子，表明骨髓瘤可诱导其表达。骨髓中表达的一些细胞因子在存在地塞米松的情况下可诱导骨髓瘤增殖，这表明骨髓瘤对这些细胞因子存在依赖性。我们的数据表明，骨髓瘤细胞在骨髓腔内增殖多于在其他器官，并非因为“归巢”至骨髓，而是由于骨髓细胞组成性表达的生长因子。随着骨髓瘤的进展，我们观察到脾细胞中生长因子表达的诱导。此外，由于除IL-6之外的细胞因子也可能诱导骨髓瘤细胞增殖，因此旨在中和IL-6的治疗可能不是治疗该疾病的最有效方法。这些发现对多发性骨髓瘤的病理生理学和治疗均具有重要意义。
