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一种抑制多种癌细胞系促凝血活性的单克隆抗体的产生。

Generation of a monoclonal antibody that inhibits the procoagulant activity of various cancer cell lines.

作者信息

Inufusa H, Adachi T, Suzuki M, Ando O, Ohta T, Kurimoto M, Nakatani Y, Nakamura M, Yasutomi M

机构信息

The First Department of Surgery, Kinki University School of Medicine, Osaka, Japan.

出版信息

Cancer. 1998 Apr 15;82(8):1563-9. doi: 10.1002/(sici)1097-0142(19980415)82:8<1563::aid-cncr19>3.0.co;2-2.

Abstract

BACKGROUND

Tumor procoagulant is one of the factors responsible for disseminated intravascular coagulation and metastasis. The authors found procoagulant activity in LK52 human squamous cell carcinoma cells, which they designated cancer cell-derived blood coagulating activity 1 (CCA-1). A monoclonal antibody (MoAb) was generated to characterize this CCA-1 procoagulant activity. To date, antibodies that show an inhibitory effect on procoagulant activity as well as high reactivity in cancer cells are well known for their tissue factor specificity.

METHODS

Characterization of the procoagulant activity of CCA-1 was performed and an anti-CCA-1 MoAb, FS01, was generated. CCA-1 expression on the cancer cell surface was examined by flow cytometry. Procoagulant activity of various cancer cell lines and the inhibitory effect of the FS01 MoAb on this procoagulant activity was monitored by a clot timer.

RESULTS

The enzymologic character differed from that of cancer procoagulant (CP). The FS01 MoAb inhibited the procoagulant activity of CCA-1, but did not inhibit that of tissue factor. A positive correlation was observed between the expression intensity of CCA-1 and the inhibitory effect of the FS01 MoAb on the procoagulant activity of cancer cell lines. Expression of CCA-1 was observed more frequently than that of tissue factor in human cancer cell lines.

CONCLUSIONS

The FS01 MoAb generated in the current study is a new antibody that reacts with various cancer cell lines, but not with normal cells. FS01 inhibits cancer cell-derived procoagulant activity and does not react with tissue factor and CP. CCA-1, which is recognized by the FS01 MoAb, appears to play a major role in cancer cell-derived procoagulant activity.

摘要

背景

肿瘤促凝剂是导致弥散性血管内凝血和转移的因素之一。作者在LK52人鳞状细胞癌细胞中发现了促凝活性,他们将其命名为癌细胞衍生的血液凝固活性1(CCA-1)。制备了一种单克隆抗体(MoAb)以表征这种CCA-1促凝活性。迄今为止,对促凝活性具有抑制作用且在癌细胞中具有高反应性的抗体因其组织因子特异性而闻名。

方法

对CCA-1的促凝活性进行了表征,并制备了抗CCA-1 MoAb FS01。通过流式细胞术检测癌细胞表面的CCA-1表达。使用凝血时间测定仪监测各种癌细胞系的促凝活性以及FS01 MoAb对该促凝活性的抑制作用。

结果

其酶学特性与癌促凝剂(CP)不同。FS01 MoAb抑制CCA-1的促凝活性,但不抑制组织因子的促凝活性。观察到CCA-1的表达强度与FS01 MoAb对癌细胞系促凝活性的抑制作用之间存在正相关。在人癌细胞系中,CCA-1的表达比组织因子的表达更常见。

结论

本研究中产生的FS01 MoAb是一种新的抗体,可与各种癌细胞系反应,但不与正常细胞反应。FS01抑制癌细胞衍生的促凝活性,且不与组织因子和CP反应。被FS01 MoAb识别的CCA-1似乎在癌细胞衍生的促凝活性中起主要作用。

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