Fibrinogen-like protein 2/fibroleukin prothrombinase contributes to tumor hypercoagulability via IL-2 and IFN-γ

Abstract

AIM:To examine the role of Fibrinogen-like protein 2 (fgl2)/fibroleukin in tumor development. Fgl2 has been reported to play a vital role in the pathogenesis in MHV-3 (mouse hepatitis virus) induced fulminant and severe hepatitis, spontaneous abortion, allo-and xenograft rejection by mediating "immune coagulation". METHODS: Tumor tissues from 133 patients with six types of distinct cancers and the animal tumor tissues from human hepatocellular carcinoma (HCC) model on nude mice (established from high metastasis HCC cell line MHCC97LM6) were obtained. RESULTS: Hfgl2 was detected in tumor tissues from 127 out of 133 patients as well as tumor tissues collected from human HCC nude mice.

The cell-membrane prothrombinase, fibrinogen-like protein 2, promotes angiogenesis and tumor development

“…Like the other coagulation proteins [24][25][26][27][28], FGL-2 exerts substantial pro-angiogenic activity, as indicated in the present study by the 5-fold increase in fgl-2 expression in IFN-γ-stimulated HUVEC. Accordingly, Su et al [7] reported a 10-fold increase in fgl-2 mRNA following stimulation with IFN-γ. In our experiments, HUVEC stimulated with IFN-γ exhibited significant capillary tube formation on ECMatrix whereas fgl-2-silenced HUVEC did not.…”

“…A recent study found that knockdown of FGL-2 delayed tumor growth and angiogenesis in mice injected with the human hepatocellular carcinoma (HCC) cell line [18]. The authors hypothesized that the protumorigenic activity of FGL-2 is a result of FGL-2-induced generation of thrombin leading to thrombin-induced tumorigenesis [7,18]. However, this does not explain the upregulation of FGL-2 in tumor cells.…”

“…Overexpression of FGL-2 has been detected in tumor and interstitial inflammatory cells but not in the normal surrounding tissue [7]. A recent study found that knockdown of FGL-2 delayed tumor growth and angiogenesis in mice injected with the human hepatocellular carcinoma (HCC) cell line [18].…”

“…One potential candidate is the cell-membrane-associated protein, fibrinogen-like protein 2 (FGL-2)/fibroleukin, which has been shown to induce sprouting in vascular endothelial cells [6] and to be overexpressed in tumor cells [7]. FGL-2, also known as FGL-2-prothrombinase, is a member of the fibrinogen family of proteins [8].…”

Cancer and thrombosis: a fresh look at an old story

“…FGL-2, a member of the fibrinogen family of proteins, is a transmembrane prothrombinase exerting serine protease activity that is capable of converting prothrombin to thrombin in the absence of factor VII or factor X [15]. FGL-2 has been shown to be involved in angiogenesis and it was found to be overexpressed in tumor cells [16,17]. The exact role of FGL-2 in tumor development however, has not been fully elucidated yet.…”