von Schweinitz D, Schmidt D, Fuchs J, Welte K, Pietsch T
Department of Pediatric Surgery, Medical School Hannover, Germany.
Pediatr Res. 1995 Oct;38(4):555-63. doi: 10.1203/00006450-199510000-00014.
Extramedullary hematopoiesis is a characteristic feature of hepatoblastoma (HB). We investigated 15 HB to characterize intratumoral hematopoietic foci and to find clues to the pathophysiology of their formation. By conventional histology and immunohistochemistry, we found erythroblasts in all and megakaryocytes in 10 of the HB, whereas granulocyte and monocyte precursor cells could not be identified in hematopoietic foci of any tumor. Only a minority of erythropoietic cells in these foci contained fetal Hb (HbF). We recently found that HB cells produce IL-1 beta and thus stimulate stromal cells to secrete IL-6. We therefore searched for other hematopoietic cytokines in HB. Supernatants of primary HB cultures were subjected to ELISA, bioassayed, and immunoblotted. We detected erythropoietin (EPO) in 11 of 15, stem cell factor (SCF) in 7 of 11, granulocyte colony-stimulating factor (G-CSF) in 4 of 15, granulocyte/macrophage colony-stimulating factor (GM-CSF) in 6 of 15, IL-3 in 1 of 12, leukemia inhibitory factor (LIF) in 1 of 9, and macrophage colony-stimulating factor (M-CSF) in 1 of 8 conditioned media. With immunoenzymatic labeling we localized EPO and SCF to the cytoplasm of epithelial HB cells, whereas stromal cells and cells of immature fibrous tissue of mixed HB expressed SCF, G-CSF, GM-CSF, LIF, and M-CSF. EPO and SCF could also be detected in extracts of epithelial HB cells. We conclude that, in HB, erythropoiesis and megakaryopoiesis but not the granulocyte-macrophage lineage is induced by fetal and embryonal tumor cells in cooperation with stromal cells by locally secreted cytokines.
髓外造血是肝母细胞瘤（HB）的一个特征性表现。我们研究了15例HB，以对肿瘤内造血灶进行特征描述，并寻找其形成的病理生理学线索。通过传统组织学和免疫组织化学方法，我们在所有HB中均发现了成红细胞，10例中发现了巨核细胞，而在任何肿瘤的造血灶中均未识别出粒细胞和单核细胞前体细胞。这些灶中只有少数造血细胞含有胎儿血红蛋白（HbF）。我们最近发现HB细胞可产生白细胞介素-1β（IL-1β），从而刺激基质细胞分泌IL-6。因此，我们在HB中寻找其他造血细胞因子。对原代HB培养物的上清液进行酶联免疫吸附测定（ELISA）、生物测定和免疫印迹分析。我们在15例中的11例中检测到促红细胞生成素（EPO），11例中的7例中检测到干细胞因子（SCF），15例中的4例中检测到粒细胞集落刺激因子（G-CSF），15例中的6例中检测到粒细胞/巨噬细胞集落刺激因子（GM-CSF），12例中的1例中检测到IL-3，9例中的1例中检测到白血病抑制因子（LIF），8例条件培养基中的1例中检测到巨噬细胞集落刺激因子（M-CSF）。通过免疫酶标记，我们将EPO和SCF定位到上皮性HB细胞的细胞质中，而混合性HB的基质细胞和未成熟纤维组织细胞表达SCF、G-CSF、GM-CSF、LIF和M-CSF。在上皮性HB细胞提取物中也可检测到EPO和SCF。我们得出结论，在HB中，胎儿和胚胎肿瘤细胞与基质细胞通过局部分泌的细胞因子协同作用，诱导了红细胞生成和巨核细胞生成，但未诱导粒细胞-巨噬细胞系的生成。
