Biological significance of fatty acid binding protein in human gastric and colonic carcinoma

1. 肝型脂肪酸结合蛋白（L-FABP）在胃癌（n=667）和肺癌（n=199）中的表达频率分别为38%和60%。两种癌中L-FABP的表达与脂肪酸合成酶（FAS）、临床病理因素及患者生存率无相关性。在肺癌中，L-FABP的表达与血管内皮生长因子的表达密切相关，提示L-FABP可能与脂肪酸从血液中摄取有关。胃癌中心脏型（H-） FABP的表达频率为19%，其表达与FAS表达、淋巴结转移、肝转移等临床病理因素及患者生存期有良好的相关性。由此可见，H-FABP似乎参与了fas合成脂肪酸的细胞内代谢途径。L-FABP在正常胃上皮中未发现，但在化生上皮和腺瘤中分别占90%和38%。因此，L-FABP在胃癌癌前阶段表达。与L-FABP相比，H-FABP在正常和瘤前（化生和腺瘤）胃粘膜中均未观察到。L-FABP和H-FABP在结肠癌中的表达目前正在研究中。4种结肠癌细胞系和8种胃癌细胞系中有6种产生H-FABP，而12种细胞系中只有TKGW胃癌细胞系产生L-FABP。通过二维凝胶电泳和western blotting，在正常肝脏中可见3个斑点，在TKGW细胞中提取的L-FABP可见4个斑点，在肝脏中可见1个斑点。棕榈酸酯（1.9x10^<-4> mol/L ~ 7.5x10^<-4> mol/L）对胃癌细胞和结肠癌细胞的影响未见明显形态学改变、脂肪堆积和生长迟缓。

1. Liver-type fatty acid-binding protein (L-FABP) was expressed in gastric carcinoma (n=667) at 38% and lung carcinoma (n=199) at 60% in frequency, respectively. Expression of L-FABP was not associated with that of fatty acid synthase (FAS), clinicopathologic factors and patient survival in these two carcinomas. In lung carcinoma, L-FABP expression showed close association with that of vascular endothelial growth factor, suggesting possible role of L-FABP in fatty acid uptake from blood stream.2. Expression of heart-type (H-) FABP was observed at 19% in frequency in gastric carcinoma, and its expression revealed good correlation with expression of FAS, clinicopathologic factors including lymph node metastasis and hepatic metastasis, and patient survival. From these, H-FABP seems to be involved in intracellular metabolic pathway(s) of fatty acid(s) synthesized by FAS.3. L-FABP was not found in normal gastric epithelium but found at 90% in metaplastic epithelium and 38% in adenoma in frequency. Therefore L-FABP was expressed in precancerous stage of stomach carcinoma.4. In contrast with L-FABP, H-FABP was observed in neither normal nor preneoplastic (metaplasia and adenoma) gastric mucosa.5. Expression of L-FABP and H-FABP in colon carcinoma is now under investigation.6. Four colon cancer cell lines and six out of eight stomach cancer cell lines produced H-FABP, while only TKGW gastric cancer cell line produced L-FABP among 12 cell lines examined.7. By two dimensional gel electrophoresis and western blotting, three spots were formed in normal liver L-FABP, while four spots, one additional spot to those in liver L-FABP, were observed in L-FABP extracted from TKGW cells.8. Treatment with palmitate (1.9x10^<-4>- 7.5x10^<-4> mol/L) of gastric cancer cells and colon cancer cells revealed no remarkable morphological change, fat accumulation and growth retardation of cancer cells.