Studies on immuno-chemotherapy regulating metastatic factors in head and neck carcinomas

以往的多学科综合治疗未能改善晚期头颈部恶性肿瘤的不良预后。患者的免疫功能恶化以及肿瘤细胞的生物学活性可能导致这种不良结局。利用建立的头颈部鳞状细胞癌细胞系，我们研究了这些肿瘤细胞的生物学活性。肿瘤细胞对TNF-α敏感，而对5-FU敏感性较低，部分头颈部肿瘤细胞分泌G-CSF。由不能分泌G-CSF的细胞刺激的效应细胞对两种自体肿瘤细胞系均未显示出裂解能力。用该肿瘤细胞刺激后的上清液包含TGF-β 1。研究的细胞系中有一半表达ICAM-1抗原， 关于我们 IFN-γ的作用。ICAM-1在肿瘤细胞上的表达程度与化疗的临床疗效相关。而肿瘤细胞培养上清中含有纤维连接蛋白样物质和碱性成纤维细胞生长因子，纤维连接蛋白样物质的高表达与化疗疗效差有关，碱性成纤维细胞生长因子的高表达与化疗疗效高有关。使用HUVEC，分析了血行转移的初始步骤。流动条件下T细胞的滚动依赖于内皮细胞表达的E-选择素和P-选择素，但不依赖于ICAM-1的表达。而肿瘤细胞的粘附则依赖于内皮细胞表面ICAM-1的表达和选择素家族的表达。生长因子如bFGF和EGF对肿瘤细胞生长和转移的生物学影响，以及适当的免疫化疗是否会改变生物学能力正在研究中。少

The past multidisciplnary treatments have not been able to improve the poor prognosis of advanced head and neck carcinomas. The immunological deterioration in patients and, also, the biological activities of tumor cells might cause this poor outcome. Using established cell lines derived from head and neck squamous cell carcinomas, we studied the biological activities of these tumor cells. There were sensitive tumor cells to TNF-alpha, whereas these tumor cells showed a relatively low sensitivity to 5-FU.Otherwhile some head and neck tumor cells secreted G-CSF.From a patient, both a cell line incapable of secreting G-CSF and a cell line capable of secreting G-CSF were established. The effector cells stimulated by the cells incapable of secreting G-CSF did not show a lytic capacity against both autologous tumor cell lines. The supernatant after the stimulation with this tumor cells included TGF-beta1. The half of studied cell lines expressed ICAM-1 antigen which was augmented by the addi … More tion of IFN-gamma. The degree of ICAM-1 expression on tumor cells had a correlation with the clinical response to chemotherapy. On the other hand, the supernatant of tumor cells included fibronectin like-substance and bFGF.The high expression of fibronectin like-substance in the supernatant correlated with the poor response to chemotherapy and that of the latter one showed a relationship with high response to chemotherapy. Using HUVECs, an initial step of hematogenous metastasis was analyzed. The rolling of T cells under flow conditions was dependent on E-selectin as well as P-selectin expressed on endotherial cells, but not on ICAM-1 expression. In contrast, the adhesion of tumor cells was dependent on ICAM-1 expression on endotherial cells as well as expression of selectin family. The biological influence of growth factors, e.g.bFGF and EGF,on the growth and metastasis of tumor cells, and whether the adequate immuno-chemotherapy would modify the biological capacity are under investigation. Less