Fibrinogen mediates bladder cancer cell migration in an ICAM-1-dependent pathway

Abstract

SummaryFibrinogen (fg), present in tumor matrices, has been demonstrated to be determinant in metastatic potential. We have recently shown that fg/ICAM-1 interactions are involved in leukocyte migration across endothelial cell monolayers. Using bladder transitional cell carcinoma as a model, we will show in this study that bladder high grade tumor cell lines express ICAM-1, and that this expression induces an fg-mediated migration. This phenomenon was dependent on ICAM-1/fg interaction as well as RhoA activity. ICAM-1 was concentrated in focal adhesion plaques when tumor cells were allowed to adhere on immobilized fg, suggesting a role in cell migration. The addition of fg induced a 3- to 6-fold enhancement of bladder tumor cell migration through HUVEC monolayers. This process was inhibited by an anti-ICAM-1 antibody blocking fg binding, demonstrating that ICAM-1/fg interaction was involved in the extravasation process. Finally, immunohistological studies revealed that the expression of ICAM-1 was closely associated with an infiltrative histological phenotype.Part of this paper was originally presented as part of the joint meetings of the 16th International Congress of the International Society of Fibrinolysis and Proteolysis (ISFP) and the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.

Effect of mild hypothermia on breast cancer cells adhesion and migration

“…The targeting of inflammatory mediators (chemokines and cytokines, such as TNF-α and IL-1β), key transcription factors involved in inflammation (such as NF-κB and STAT3) or inflammatory cells decreases the incidence and spread of cancer (40). In various cancers, ICAM- 1 expression is at an elevated level and is associated with the malignant potential of cancer (5)(6)(7)(8)(9). To some extent, ICAM-1 overexpression is associated with the inflammatory environment in tumors.…”

“…ICAM-1 is widely expressed at a low basal level and is upregulated by inflammatory cytokines (TNF-α, IL-1, IFN-γ) in endothelial cells. In various cancers, such as non-small cell lung cancer (5), breast cancer (6), gastric cancer (7), colorectal cancer (8), and bladder cancer (9), ICAM-1 expression is at an elevated level and is associated with the malignant potential of cancer. Increasing evidence suggest that ICAM-1 plays an important role in the adhesion of tumor cells to endothelial cell monolayers and subsequent transendothelial migration (10)(11)(12)(13).…”

Evidence of a Functional Role for Interaction between ICAM-1 and Nonmuscle α-Actinins in Leukocyte Diapedesis

“…These proteins act upon several actin-associated proteins including heat shock protein 27, cortactin, focal adhesion kinase, paxillin, and p 130 Cas which may in turn influence actin cytoskeleton (33,35,36). Furthermore, ICAM-1 signaling can also be initiated through ligation by fg (37,38), a ligand of ICAM-1 which increases neutrophil transmigration across endothelium when associated to ICAM-1 (21,39). Finally, an original approach using peptidomimetics of the ICAM-1 intracellular domain further suggests that ICAM-1 mediates signaling events during lymphocyte migration across brain EC (18).…”

The Role of Fibrin(ogen) in Transendothelial Cell Migration During Breast Cancer Metastasis

“…Fibrin(ogen) potentiates FGF-2-but not VEGF-induced proliferation of endothelial cells, angiogenesis and cancer cell growth (Rybarczyk & Simpson-Haidaris, 2000;Sahni & Francis, 2000;Sahni et al, 2006;Sahni et al, 2008;Sahni et al, 1999;Simpson-Haidaris, 1997;Simpson-Haidaris & Rybarczyk, 2001). Furthermore, fibrin(ogen) enhances cell migration and cancer invasion through tumor stroma, and TEM, i.e., intravasation of breast cancer cells into the blood stream (Step 3) (Roche et al, 2003;Rybarczyk et al, 2003;Sahni et al, 2009). Fg and fibrin can bridge between cells of the same or different kinds (Kloczewiak et al, 1983;Languino et al, 1995;Languino et al, 1993;Saito et al, 2002;Sriramarao et al, 1996) and form aggregates or tumor emboli coated with fibrin(ogen) (Step 4).…”