Submission 44
Citrullination of fibrinogen creates a pre-metastatic site to facilitate lung metastasis in cancer patients
Tuesday-Talks 3-Selected talk-04
Presented by: Takeshi Tomita
Tumor metastasis is one of the most challenging problems in cancer research. It is estimated that 90% of cancer-related deaths are due to metastasis, and the study of metastasis is needed. Tumor metastasis results from interactions between the primary tumor and secondary metastatic tissues. Primary tumor-derived molecular signals influence endothelial cells and immune cells in the distant organ to make the microenvironment pro-tumor. Once a circulating tumor cell reaches the microenvironment, the cell increases its chances of survival and extravasation into the tissue for tumor regrowth. Because this microenvironment formation occurs before the tumor cells physically appear, it is referred to as the pre-metastatic region. In this study, we have demonstrated [Nature Commun (2023) 14, 4096] accumulation of citrullinated fibrinogens (citFbgs) in the pre-metastatic lung using our humanized serum amyloid A (SAA) mouse model and clinical specimens. Pulmonary endothelial cells mediate citrullination of fibrinogen and citFbgs form aggregation complexes that attract tumor cells. Our specific antibody to CitFbg clearly visualized the pre-metastatic sites in the lung, and this detection is the first step towards preventing metastasis.