FIBRINOGEN-LIKE PROTEIN 2 (FGL-2) - A NOVEL BIOMARKER FOR CANCER
13 slide(s) – English – 2012-06-29
Fibrinogen-like protein 2 (FGL-2) - a novel biomarker for cancer
Rabizadeh E1, Lederfine D1,Rosenbaum E,2, Brenner B2, Inbal A3
1Hemato-Oncology Laboratory, Felsenstein Medical Research Center, 2Oncology Institute, 3Thrombosis and Hemostasis Unit, Hematology Institute, Beilinson Hospital, Davidoff Cancer Center, Sackler Faculty of Medicine Tel Aviv University, Israel
Background: Hematologic and solid tumors are associated with hypercoagulability the reason for which has not been delineated. Prothrombinase named fibrinogen-like protein 2 (FGL-2) is a 70 kD transmembrane protein that was found to have a quality of a serine protease capable of directly cleaving prothrombin to thrombin. FGL-2 is synthesized by monocytes, T-lymphocytes and endothelial cells. FGL-2 protein and its mRNA have been previously found within different tumor cells.
Aim: To study the role of FGL-2 in patients with prostate and colon cancer. Our hypothesis is that upregulation of FGL-2 activity in cancer patients may contribute to tumorigenesis via generation of thrombin leading to increased angiogenesis and spread/metastasis of tumor cells.
Methods: Thrombin generation reflecting FGL-2 activity was measured in homogenized peripheral blood mononuclear cells (PBMC) from patients with prostate and colon cancer after addition of prothrombin and compared to that of normal controls. mRNA of FGL-2 was measured in PBMC and malignant cell lines by quantitative RT-PCR analysis.
Results: Above 3-fold increase in FGL-2 activity in PBMC from patients with prostate or colon cancer was observed (p<0.0001 for each) compared to that of normal controls. To validate that the prothrombinase activity found in patient’s monocytes is specific to FGL-2 this protein was immunoprecipitated (IP) and thrombin generation was measured. Three-fold increase in thrombin generation was obtained from patient’s PBMC following IP, similarly to that observed in non-IP PBMC. Increased mRNA of FGL-2 was found in PBMC from patients with prostate and colon cancer and from human prostate adenocarcinoma line (PC-3). Following treatment of HUVEC and PC-3 with INF-the amount ofmRNA increased even further. In line with this finding an increase in thrombin generation in PC-3 cell line (reflecting FGL-2 activity) was observed as well.
Conclusions: The results of this research suggest that FGL-2 may serve as a new biomarker of prostate and some colon cancers. In the future FGL-2 activity may be used as a biomarker at diagnosis and during follow up.