Franz M G, Winkler B C, Norman J G, Fabri P J, Gower W R
Department of Surgery, University of South Florida Health Sciences Center, Tampa.
Biochem Biophys Res Commun. 1994 Dec 30;205(3):1815-21. doi: 10.1006/bbrc.1994.2881.
TNF is a 17kD cytokine classically known for its cytotoxic effects on malignant cells. More recent cell culture studies demonstrated TNF induced cytostasis associated with the expression of a terminally differentiated phenotype. This was best characterized in malignant hematopoietic models, although a similar action on cells derived from solid tumors is now increasingly recognized. In the present study, six day exposure to TNF (40 ng/ml) stimulated morphologic changes in a human pancreatic adenocarcinoma cell line (HPAC), including increased cellular homogeneity, decreased nuclear to cytoplasmic ratio and detachment from the cell monolayer. Proliferation and DNA synthesis were reversibly inhibited while cellular viability was maintained. Parallel to the changes in morphology and growth was the delayed appearance of carbonic anhydrase II (CA II, E.C. 4.2.1.1), an accepted marker for pancreatic cells of ductal origin. A concomitant increase in the steady-state level of CA II mRNA was also observed over the time-course of TNF exposure. These results suggest a novel role for TNF in the induction of a more terminally differentiated ductal cell phenotype in a human pancreatic carcinoma model.
肿瘤坏死因子（TNF）是一种17kD的细胞因子，传统上以其对恶性细胞的细胞毒性作用而闻名。最近的细胞培养研究表明，TNF可诱导细胞生长停滞，并与终末分化表型的表达相关。这在恶性造血模型中表现得最为明显，不过现在人们越来越认识到它对实体瘤来源的细胞也有类似作用。在本研究中，用TNF（40 ng/ml）处理6天可刺激人胰腺腺癌细胞系（HPAC）发生形态学变化，包括细胞同质性增加、核质比降低以及从细胞单层脱离。增殖和DNA合成受到可逆性抑制，而细胞活力得以维持。与形态和生长变化同时出现的是碳酸酐酶II（CA II，E.C. 4.2.1.1）延迟出现，它是导管来源胰腺细胞的公认标志物。在TNF处理的时间进程中，还观察到CA II mRNA稳态水平随之增加。这些结果表明，TNF在人胰腺癌模型中诱导更终末分化的导管细胞表型方面具有新作用。
