TUMOR-NECROSIS-FACTOR AND ITS RECEPTORS IN HUMAN OVARIAN-CANCER - POTENTIAL ROLE IN DISEASE PROGRESSION
TUMOR-NECROSIS-FACTOR AND ITS RECEPTORS IN HUMAN OVARIAN-CANCER - POTENTIAL ROLE IN DISEASE PROGRESSION
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DOI：
10.1172/jci116446
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发表时间：
1993-05-01
影响因子：
15.9
通讯作者：
BALKWILL, FR
中科院分区：
文献类型：
--
作者：
NAYLOR, MS;STAMP, GWH;BALKWILL, FR
肿瘤坏死因子（TNF）基因在63例人类上皮性卵巢癌活检标本中的45例中表达。在浆液性肿瘤中，TNF表达水平与肿瘤分级呈正相关。TNF mRNA在上皮肿瘤细胞和浸润性巨噬细胞中发现，而TNF蛋白主要定位于肿瘤区域内和附近的巨噬细胞亚群。p55 TNF受体基因的mRNA和蛋白定位于肿瘤上皮和肿瘤，但不定位于间质巨噬细胞。p75 TNF受体仅限于浸润细胞。在卵巢癌腹水中也发现表达TNF mRNA的细胞，在部分腹水中检测到TNF蛋白。在2/12例正常卵巢活检中，在黄体膜层的少数细胞中检测到TNF mRNA。血清TNF及其可溶性受体水平与匹配活检组织中TNF表达程度无关。北方和南方分析显示TNF基因无明显异常。肿瘤坏死因子及其受体在卵巢癌活检组织中的共表达提示其具有自分泌/旁分泌作用的能力。TNF拮抗剂可能对这种恶性肿瘤有治疗潜力。
The gene for tumor necrosis factor, TNF, was expressed in 45 out of 63 biopsies of human epithelial ovarian cancer. In serous tumors, there was a positive correlation between level of TNF expression and tumor grade. TNF mRNA was found in epithelial tumor cells and infiltrating macrophages, whereas TNF protein localized primarily to a subpopulation of macrophages within and in close proximity to tumor areas. mRNA and protein for the p55 TNF receptor gene localized to the tumor epithelium and tumor, but not to stromal macrophages. The p75 TNF receptor was confined to infiltrating cells. Cells expressing TNF mRNA were also found in ovarian cancer ascites and TNF protein was detected in some ascitic fluids. In 2 out of 12 biopsies of normal ovary, TNF mRNA was detected in a minority of cells in the thecal layer of the corpus luteum. Serum levels of TNF and its soluble receptor did not correlate with extent of TNF expression in matched biopsies. Northern and Southern analysis revealed no gross abnormality of the TNF gene. The coexpression of TNF and its receptor in ovarian cancer biopsies suggests the capacity for autocrine / paracrine action. TNF antagonists may have therapeutic potential in this malignancy.