Effect of thrombin treatment of tumor cells on adhesion of tumor cells to platelets in vitro and tumor metastasis in vivo.
Effect of thrombin treatment of tumor cells on adhesion of tumor cells to platelets in vitro and tumor metastasis in vivo.
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发表时间：
1992-06
期刊：
影响因子：
11.2
通讯作者：
M. Nierodzik;F. Kajumo;S. Karpatkin
中科院分区：
文献类型：
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作者：
M. Nierodzik;F. Kajumo;S. Karpatkin
7种不同的肿瘤细胞系(人黑色素瘤SK Mel 28；仓鼠黑色素瘤HM29；小鼠黑色素瘤B16F10和无色素性黑色素瘤B16a；人结肠癌HCT8；小鼠结肠癌CT26和小鼠Lewis肺癌)以0.5-1单位/毫升的凝血酶处理并检测它们与黏附的血小板的结合能力；研究HM29与纤维连接蛋白和von Willebrand因子的结合能力；CT26、B16F1、B16F10和B16a静脉注射后形成肺转移的能力。注射凝血酶处理的肿瘤细胞；研究CT26的生长能力。7个经凝血酶治疗的肿瘤细胞系中有5个将其与黏附的血小板的粘附性增加了2-3倍。HM29使其对纤维连接蛋白和von Willebrand因子的粘附率增加2-3倍。CT26、B16F1、B16F10和B16a可使实验性肺转移增加10-156倍。经凝血酶处理后的CT26细胞在体内的生长速度是S.C.注射。凝血酶治疗的肿瘤细胞增强与血小板的黏附的机制需要血小板整合素GPIIb-GPIIIa，因为它可以被已知阻断配体与GPIIb-GPIIIa的黏附的药物(单抗10E5，四肽RGDS，去整合素Albolabrin)抑制；以及在肿瘤细胞上的“GPIIb-GPIIIa样”结构，因为它可以被凝血酶治疗的肿瘤细胞用10E5和RGDS抑制。凝血酶作用于肿瘤细胞1h效果最好，不需要肿瘤细胞表面活性凝血酶，也不需要蛋白质合成(放线菌素不抑制)。因此，凝血酶处理的肿瘤细胞显著增强了肺转移。这可能是凝血酶诱导的粘附性增强和肿瘤细胞生长的继发性作用。
Seven different tumor cell lines (human melanoma SK MEL 28; hamster melanoma HM29; murine melanomas B16F10 and amelanotic melanoma B16a; human colon carcinoma HCT8; murine colon carcinoma CT26; and murine Lewis lung carcinoma) were treated with thrombin at 0.5-1 unit/ml and examined for their ability to bind to adherent platelets; HM29 was studied for its ability to bind to fibronectin and von Willebrand factor; CT26, B16F1, B16F10, and B16a were studied for their ability to form pulmonary metastasis after i.v. injection of thrombin-treated tumor cells; CT26 was studied for its ability to grow s.c. Five of 7 thrombin-treated tumor cell lines increased their adhesion to adherent platelets 2-to 3-fold. HM29 increased its adherence to fibronectin and von Willebrand factor 2- to 3-fold. CT26, B16F1, B16F10, and B16a increased experimental pulmonary metastasis 10- to 156-fold. Thrombin-treated CT26 cells demonstrated 2-fold greater growth in vivo after s.c. injection. The mechanism of enhanced adhesion of thrombin-treated tumor cells to platelets required the platelet integrin GPIIb-GPIIIa since it could be inhibited by agents known to block adhesion of ligands to GPIIb-GPIIIa (monoclonal antibody 10E5, tetrapeptide RGDS, disintegrin Albolabrin); as well as a "GPIIb-GPIIIa-like" structure on tumor cells since it could be inhibited by treatment of thrombin-treated tumor cells with 10E5 and RGDS. The thrombin effect on tumor cells was optimum at 1 h of incubation with thrombin, did not require active thrombin on the tumor cell surface, and did not require protein synthesis (not inhibited by cycloheximide). Thus, thrombin-treated tumor cells markedly enhance pulmonary metastasis. It is suggested that this may be secondary to thrombin-induced enhanced adhesion as well as growth of tumor cells.