Hemato-Oncology Laboratory, Felsenstein Medical Research Center, Petah Tikva, Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Hematology Laboratory, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel.
PLoS One. 2023 May 18;18(5):e0285735. doi: 10.1371/journal.pone.0285735. eCollection 2023.
Fibrinogen-like protein 2 (FGL2) is a serine protease capable of converting prothrombin into thrombin (i.e., prothrombinase-like activity) while bypassing the classic coagulation cascade. It has been reported to be expressed by mononuclear blood cells and endothelial cells. There are multiple reports that FGL2 supports tumor development and metastasis. However, in the blood, the origin and functional significance of FGL2 has not been established.
To determine if FGL2, a malignancy related enzyme, is present in platelets.
Peripheral blood samples were collected in K2 EDTA tubes. Blood cells and platelets were separated and thoroughly washed to produce plasma-free samples. Procoagulant activity was measured in the cell lysates using a thrombin generation test or an adjusted prothrombin time (PT) test in plasma deficient of factor X. The findings were further supported by confocal microscopy, immunoprecipitation, flow cytometry, enzyme-linked immunosorbent assays and specific inhibition assays.
FGL2 protein was readily detected in platelets. Also, despite being expressed by lymphocytes, FGL2 prothrombinase-like activity was solely detected in platelet samples, but not in white blood cell samples. Quiescent platelets were shown to contain the FGL2 protein in an active form. Upon activation, platelets secreted the active FGL2 into the milieu.
Active FGL2 is found in platelets. This suggests another role for the involvement of platelets in malignancies.
纤维蛋白原样蛋白 2（FGL2）是一种丝氨酸蛋白酶，能够将凝血酶原转化为凝血酶（即凝血酶原酶样活性），同时绕过经典的凝血级联反应。据报道，它由单核血细胞和内皮细胞表达。有多项报道表明 FGL2 支持肿瘤的发生和转移。然而，在血液中，FGL2 的来源和功能意义尚未确定。
确定与恶性肿瘤相关的酶 FGL2 是否存在于血小板中。
采集外周血样本于 K2 EDTA 管中。分离血细胞和血小板，并彻底清洗以产生无血浆的样本。使用凝血酶生成试验或在缺乏因子 X 的血浆中调整的凝血酶原时间（PT）试验测量细胞裂解物中的促凝活性。共聚焦显微镜、免疫沉淀、流式细胞术、酶联免疫吸附试验和特异性抑制试验进一步支持了这些发现。
FGL2 蛋白在血小板中很容易被检测到。此外，尽管 FGL2 在淋巴细胞中表达，但 FGL2 凝血酶原酶样活性仅在血小板样本中检测到，而在白细胞样本中未检测到。研究表明，静止的血小板中含有处于活性形式的 FGL2 蛋白。血小板激活后，会将活性 FGL2 分泌到细胞外环境中。
活性 FGL2 存在于血小板中。这表明血小板可能在恶性肿瘤中发挥了另一种作用。
