Dippold W G, Klingel R, Kerlin M, Schwaeble W, Meyer zum Büschenfelde K H
Department of Internal Medicine I, Johannes Gutenberg-Universität Mainz, Germany.
Gastroenterology. 1991 May;100(5 Pt 1):1338-44.
Hematopoietic growth factors have recently been well characterized by complementary DNA cloning. For human epidermal growth factor, granulocyte-macrophage colony-stimulating factor recombinant proteins have been expressed in Escherichia coli. To reduce the toxic side effects of chemotherapy on the bone marrow, recombinant human granulocyte-macrophage colony-stimulating factor and recombinant human interleukin 3 were applied to patients suffering of gastrointestinal cancers. To determine the influence of recombinant human granulocyte-macrophage colony-stimulating factor and recombinant human interleukin 3 on human pancreas and gastric cancer cell cells in vitro, a sensitive microculture test system was established that allows precise quantification of proliferation. A more than twofold enhancement of proliferation was observed by interleukin 3 and granulocyte-macrophage colony-stimulating factor in two of two cell cultures derived from gastric carcinoma cells, while two of nine cultures from pancreas carcinoma cells have shown enhanced cell growth in the presence of recombinant human interleukin 3 or recombinant human granulocyte-macrophage colony-stimulating factor. In comparison, recombinant human epidermal growth factor increased cell growth in two of two gastric and in five of nine pancreas carcinoma cultures. In general, 1-10 ng/mL of the growth factors yielded the highest growth rate, but even 1-pg amounts produced increased cell growth. Expression of messenger RNA for granulocyte-macrophage colony-stimulating factor, interleukin 3, and the oncogene HER2/neu remained undetectable in all of the tested cell lines, while the various abundance of messenger RNA for the epidermal growth factor receptor was different in each cell line. The reported results imply that the hematopoietic growth factors interleukin 3 and granulocyte-macrophage colony-stimulating factor influence cellular growth of pancreas and gastric carcinoma cells by a paracrine mechanism and may possess a more general regulatory function than originally anticipated.
造血生长因子最近已通过互补DNA克隆得到充分表征。对于人表皮生长因子，粒细胞巨噬细胞集落刺激因子重组蛋白已在大肠杆菌中表达。为了降低化疗对骨髓的毒副作用，重组人粒细胞巨噬细胞集落刺激因子和重组人白细胞介素3被应用于胃肠道癌症患者。为了在体外确定重组人粒细胞巨噬细胞集落刺激因子和重组人白细胞介素3对人胰腺和胃癌细胞的影响，建立了一种敏感的微量培养测试系统，该系统可精确量化增殖情况。在源自胃癌细胞的两种细胞培养物中，白细胞介素3和粒细胞巨噬细胞集落刺激因子使增殖增强了两倍以上，而在源自胰腺癌细胞的九种培养物中，有两种在重组人白细胞介素3或重组人粒细胞巨噬细胞集落刺激因子存在的情况下显示出细胞生长增强。相比之下，重组人表皮生长因子在两种胃癌培养物中的两种以及九种胰腺癌培养物中的五种中增加了细胞生长。一般来说，1 - 10 ng/mL的生长因子产生最高的生长速率，但即使是1 pg的量也能促进细胞生长。在所有测试的细胞系中均未检测到粒细胞巨噬细胞集落刺激因子、白细胞介素3和癌基因HER2/neu的信使RNA表达，而表皮生长因子受体的信使RNA在每个细胞系中的丰度各不相同。所报道的结果表明，造血生长因子白细胞介素3和粒细胞巨噬细胞集落刺激因子通过旁分泌机制影响胰腺和胃癌细胞的生长，并且可能具有比最初预期更广泛的调节功能。
