Camby I, Salmon I, Danguy A, Pasteels J L, Brotchi J, Martinez J, Kiss R
Laboratory of Histology, Faculty of Medicine, Free University of Brussels, Belgium.
J Natl Cancer Inst. 1996 May 1;88(9):594-600. doi: 10.1093/jnci/88.9.594.
Gastrin and cholecystokinin (CCK) mediate their effects through at least two types of receptors (CCK receptors A and B). While it has been hypothesized that gastrin, a stimulator of gastric acid secretion, is also a neurotransmitter and a stimulator of cell proliferation in various normal and neoplastic tissues, its effect on astrocytic brain tumors has not been actively investigated.
Our goal was to determine the effects of gastrin and gastin and/or CCK antagonists on the proliferation in vitro of astrocytic tumor cells by use of both established cell lines and primary cell cultures of tumor tissue.
Ten established astrocytic tumor cell lines, SW1088, SW1783, Hs683, H4, U87, U118, U138, U373, T98G, and A172, were studied. The effects of added gastrin (at 0.01, 0.1, and microM) and the gastrin/CCK antagonists L-365,260, CI-988, L-364,718, and JMV 234 (each at 0.01, 0.1, and 1 microM) on the cellular proliferation rates of the 10 cell lines were indirectly measured by use of the colorimetric tetrazolium assay. The influence of gastrin (at 0.01 microM) on the cellular proliferation of primary cultures from nine freshly explanted astrocytic tumors was assessed by means of tritiated thymidine uptake and autoradiography.
At specific concentrations, added gastrin increased the cellular proliferation of three established astrocytic cell lines (A172, Hs683, and SW1088), decreased it in two (U373 and T98G), and was without effect on the remaining five. Gastrin decreased cellular proliferation in one primary astrocytic tumor cell culture, stimulated it in five, and had no apparent effect in the remaining three. L-365,260, a CCK receptor B antagonist used at 0.01 microM, increased cellular proliferation in seven cell lines (A172, H4, Hs683, SW1783, T98G, U118, and U138), decreased it in one (U87), and had no effect in the remaining two. CI-988, another CCK receptor B antagonist used at 0.01 microM, inhibited cellular proliferation in five cell lines (A172, H4, SW1783, U373, and U87), stimulated it in two (T98G and U138), and had no effect in three. The CCK receptor A antagonists L-364,718 and JMV 234, both used at 0.01 microM, affected the cellular proliferation of only three of the 10 cell lines.
These results suggest that gastrin (and perhaps CCK that belongs to the same peptide family) may play a role in the growth of a substantial proportion of human astrocytic tumors.
胃泌素和胆囊收缩素（CCK）通过至少两种类型的受体（CCK受体A和B）介导其作用。虽然有人推测，作为胃酸分泌刺激剂的胃泌素也是一种神经递质，并且是各种正常组织和肿瘤组织中细胞增殖的刺激剂，但其对星形胶质细胞脑肿瘤的影响尚未得到积极研究。
我们的目标是通过使用已建立的细胞系和肿瘤组织的原代细胞培养物，确定胃泌素以及胃泌素和/或CCK拮抗剂对星形胶质细胞瘤细胞体外增殖的影响。
研究了10种已建立的星形胶质细胞瘤细胞系，即SW1088、SW1783、Hs683、H4、U87、U118、U138、U373、T98G和A172。通过比色四氮唑测定法间接测量添加的胃泌素（浓度分别为0.01、0.1和1微摩尔）和胃泌素/CCK拮抗剂L-365,260、CI-988、L-364,718和JMV 234（浓度分别为0.01、0.1和1微摩尔）对这10种细胞系细胞增殖率的影响。通过氚标记胸腺嘧啶摄取和放射自显影评估胃泌素（浓度为0.01微摩尔）对9个新鲜切除的星形胶质细胞瘤原代培养物细胞增殖的影响。
在特定浓度下，添加的胃泌素增加了三种已建立的星形胶质细胞系（A172、Hs683和SW1088）的细胞增殖，降低了两种细胞系（U373和T98G）的细胞增殖，而对其余五种细胞系没有影响。胃泌素降低了一种原代星形胶质细胞瘤细胞培养物的细胞增殖，刺激了五种细胞培养物的细胞增殖，而对其余三种没有明显影响。0.01微摩尔浓度的CCK受体B拮抗剂L-365,260增加了七种细胞系（A172、H4、Hs683、SW1783、T98G、U118和U138）的细胞增殖，降低了一种细胞系（U87）的细胞增殖，而对其余两种没有影响。0.01微摩尔浓度的另一种CCK受体B拮抗剂CI-988抑制了五种细胞系（A172、H4、SW1783、U373和U87）的细胞增殖，刺激了两种细胞系（T98G和U138）的细胞增殖，而对三种细胞系没有影响。CCK受体A拮抗剂L-364,718和JMV 234在0.01微摩尔浓度下仅影响了10种细胞系中的三种细胞系的细胞增殖。
这些结果表明，胃泌素（可能还有属于同一肽家族的CCK）可能在相当一部分人类星形胶质细胞瘤的生长中起作用。
