Studies on hemopoietic factors produced by human neoplasms.

为了研究肿瘤伴发白细胞增多的发病机制，从肿瘤和白细胞增多的病例中，建立了11株可移植到裸鼠体内的人肿瘤细胞系。这些肿瘤包括口腔癌、甲状腺癌、肺癌和胰腺癌、平滑肌肉瘤和与慢性粒细胞白血病相关的髓母细胞瘤，这些肿瘤的提取物在体外具有脑脊液活性。从口腔癌培养细胞系中分离纯化的粒细胞集落刺激因子(G-CSF)在体内表现出明显的中性粒细胞活性，在体外表现出明显的G-CSF活性。体外中和脑脊液活性的兔抗G-CSF抗体在原始细胞系的内质网和核周间隙内可见反应产物。这些结果表明，人类肿瘤产生的G-CSF直接刺激宿主骨髓细胞，诱导中性粒细胞增多。此外，荷髓母细胞瘤和平滑肌肉瘤裸鼠的脾淋巴细胞、B细胞、浆细胞和血清IgM水平均显著升高。髓母细胞瘤短期培养上清液对小鼠B细胞具有抗BCGF-1活性。以上结果表明，人类肿瘤能够产生多种向髓系和淋巴系分化的生长因子，可移植到裸鼠体内的人肿瘤为研究肿瘤产生的造血因子提供了有用的研究资源。

For studying the pathogenesis of leukocytosis occasionally associated with neoplasia, 11 lines of human tumor transplantable to nude mice were established from cases with neoplasia and leukocytosis more than <10^4> / <mm^3> . These tumors included carcinoma originated from oral cavity, thyroid, lung and pancreas, leiomyosarcoma and myeloblastoma associated with CML and the extracts of these tumors showed CSF activity in vitro. A granulocyte colony stimulating factor (G-CSF) purified from the culture cell line of above oral cavity carcinoma showed prominent neutrophilia in vivo as well as G-CSF activity in vitro. The rabbit antibody to G-CSF which neutralized CSF activity in vitro demonstrated reaction products within endoplasmic reticulum and perinuclear space of original cell line. These findings indicates that G-CSF produced by human tumors directly stimulates host bone marrow cells and induces neutrophilic granulocytosis. In addition, nude mice bearing myeloblastoma and leiomyosarcoma showed prominent increase in splenic lymphocytes, B cells, plasma cells and serum IgM level. The supernatant of myeloblastoma in short term culture showed BCGF- <I> activity to mouse B cells triggered by anti- <mu> antibody.Above results demonstrate that human neoplasms are able to produce various growth and differentiating factors to myeloid and lymphoid series and the human tumors transplantable to nude mice provide useful research resources for the study of hemopoietic factors produced by neoplasms.