Fibrinogen synthesized by cancer cells augments the proliferative effect of fibroblast growth factor‐2 (FGF‐2)

Sahni, Abha; Simpson-Haidaris, Patricia J.; Sahni, Sanjeev K.; Vaday, Gayle G.; Francis, Charles W.

doi:10.1111/j.1538-7836.2007.02808.x

Cited by 202 publications

(159 citation statements)

References 47 publications

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“…In line with previous publications (Wernert et al, 2007;Sahni et al, 2008), we observed that FGF-2 treatment of prostate cancer cells DU145 and PC3 stimulates proliferation and migration, respectively, as shown by cell growth evaluation and scratch-wound assay ( Supplementary Figures 2c and d). By luciferase assay, we demonstrated FGF-2 and FGFR1 as new direct targets of miR-15 and miR-16 (Supplementary Figure 2e).…”

Section: Fgf-2 and Fgfr1 Are New Targets Of Mir-15 And Mir-16supporting

confidence: 92%

Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer

et al. 2011

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The interaction between cancer cells and microenvironment has a critical role in tumor development and progression. Although microRNAs regulate all the major biological mechanisms, their influence on tumor microenvironment is largely unexplored. Here, we investigate the role of microRNAs in the tumor-supportive capacity of stromal cells. We demonstrated that miR-15 and miR-16 are downregulated in fibroblasts surrounding the prostate tumors of the majority of 23 patients analyzed. Such downregulation of miR-15 and miR-16 in cancer-associated fibroblasts (CAFs) promoted tumor growth and progression through the reduced post-transcriptional repression of Fgf-2 and its receptor Fgfr1, which act on both stromal and tumor cells to enhance cancer cell survival, proliferation and migration. Moreover, reconstitution of miR-15 and miR-16 impaired considerably the tumor-supportive capability of stromal cells in vitro and in vivo. Our data suggest a molecular circuitry in which miR-15 and miR-16 and their correlated targets cooperate to promote tumor expansion and invasiveness through the concurrent activity on stromal and cancer cells, thus providing further support to the development of therapies aimed at reconstituting miR-15 and miR-16 in advanced prostate cancer.

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Section: Fgf-2 and Fgfr1 Are New Targets Of Mir-15 And Mir-16supporting

confidence: 92%

Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer

et al. 2011

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“…We have shown that lung, prostate and breast cancer epithelial cells synthesize and secrete Fg that enhances FGF-2-mediated cell proliferation, assembles into extracellular matrices and binds to cancer cell surfaces. 2,14,[32][33][34][35][36][37] In addition, others have demonstrated Fg production in adenocarcinoma cell lines of cervical 15 and intestinal 16 origin. Recent expression array profiling studies have confirmed that the Fg genes are expressed in breast 17 and lung carcinomas 18,19 isolated from patients.…”

Section: Discussionmentioning

confidence: 99%

“…Both MoAbs T2G1 (anti-FgBb [15][16][17][18][19][20][21] ) and BV9 (anti-VE-cadherin EC3-EC4), but not MoAb 18C6 (anti-FPB Bb [1][2][3][4][5][6][7][8][9][10][11][12][13][14], partially inhibited Fg-induced FITCDextran Flux, implicating VE-cadherin and Fg-b in mechanisms of Fg-induced EC permeability. Fg is capable of inducing permeability of different types of barrier EC, as Fg also induced permeability of a microvascular EC barrier, whereas it did not induce permeability of an epithelial cell barrier.…”

Section: Discussionmentioning

confidence: 99%

“…14,[26][27][28] Control experiments indicated that Fg added to breast cancer or endothelial cells was not processed further by protease degradation or crosslinking to higher ordered structures (data not shown). Synthetic peptides corresponding to the Fg b-chain primary structure were custom synthesized as previously described, 11 and include b , b [15][16][17][18][19][20][21][22][23][24][25][26][27] , b 18-31 and b [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] (Table I).…”

Section: Fibrinogen Purification and Synthetic Peptidesmentioning

confidence: 99%

“…10 Furthermore, exposure of the b 15-42 domain mediates fibrin binding to EC surfaces, 11 promotes EC adhesion and spreading, 12 and stimulates proliferation of EC, fibroblasts and cancer cells. 13,14 Cadherins mediate homophilic cell-cell adhesion critical for the maintenance of barrier integrity of epithelium (E-cadherin) and endothelium (VE-cadherin). Breakdown of VE-cadherin-mediated endothelial barrier function leads to altered vascular permeability and remodeling, which are associated with a number of disease processes including ischemia-reperfusion injury, inflammation, angiogenesis, and cancer growth and metastasis.…”

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confidence: 99%

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The VE‐cadherin binding domain of fibrinogen induces endothelial barrier permeability and enhances transendothelial migration of malignant breast epithelial cells

Sahni

Arévalo

Sahni

et al. 2009

Intl Journal of Cancer

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Fibrin deposition and exudation of plasma fibrinogen (Fg) have long been recognized as hallmarks of inflammation, cardiovascular disease and neoplasia. The Fg-b 15-42 domain binds to the endothelial cell adhesion molecule, VE-cadherin, promoting endothelial cell proliferation, angiogenesis and leukocyte diapedesis. Furthermore, spontaneous blood-borne and lymphatic metastasis of some types of tumor emboli requires plasma fibrin(ogen); however, the molecular mechanisms by which this occurs are poorly understood. We sought to determine whether Fg-b 15-42 and VEcadherin binding interactions promote endothelial barrier permeability and breast cancer cell transendothelial migration (TEM) using transwell insert culture systems. Synthetic peptides containing/missing residues b 15-17 critical for In 1865, Armand Trousseau reported the observation that patients with an increased incidence of coagulopathies would later manifest visceral malignancies, which became known as Trousseau's syndrome. Ironically, Trousseau diagnosed himself with his own syndrome in 1866 and died of gastric cancer the following year. Causal factors linked to the prothrombotic state of Trousseau's syndrome also facilitate cancer metastasis, including thrombin, tissue factor, selectins, platelets, endothelial cells (EC) and fibrin. 1 Deposition of fibrinogen (Fg) 5 and fibrin commonly occurs within the stroma of most solid tumors, 2 and elevated levels of plasma Fg and fibrin degradation products (FDPs) correlate positively with lymph node involvement and metastasis of colon, ovarian, lung and breast cancers. 1 Studies by Degen and co-workers 3-5 have firmly established that plasma fibrin(ogen) and platelets play critical roles in spontaneous cancer metastasis through both the circulation and lymphatic systems, in part by protecting tumor cells from natural killer cell-mediated lysis.Expression of interleukin (IL)-6 during systemic inflammation upregulates expression of specific plasma proteins in the liver, including Fg. 6 Excessive fibrin deposition is accompanied by local expression of proinflammatory mediators, vascular leakage, and inflammatory cell recruitment and activation leading to amplification of the inflammatory response. 2,7,8 Residues 15-42 on the b chain of Fg have been implicated in functional attributes ascribed to fibrin(ogen). Although the primary structure of fibrinopeptide B (FPB) is poorly conserved across species, the fibrin b 15-42 domain is highly conserved, implying evolutionary conservation of function. 9 The b 15-42 region constitutes a cryptic domain in soluble Fg that is exposed in fibrin after thrombin cleavage. 10 Newly exposed residues, b15-GHRP-18, promote lateral aggregation of fibrin monomers during polymerization and insoluble clot formation in secondary hemostasis. 10 Furthermore, exposure of the b 15-42 domain mediates fibrin binding to EC surfaces, 11 promotes EC adhesion and spreading, 12 and stimulates proliferation of EC, fibroblasts and cancer cells. 13,14 Cadherins mediate homophilic cell-cell adhesion...

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Fibrinogen

Laffan¹

2010

Textbook of Hemophilia

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Fibrinogen synthesized by cancer cells augments the proliferative effect of fibroblast growth factor‐2 (FGF‐2)

Abstract: These data indicate that endogenously synthesized fibrinogen promotes the growth of lung and prostate cancer cells through interaction with FGF-2.

Cited by 202 publications

References 47 publications

Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer

Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer

The VE‐cadherin binding domain of fibrinogen induces endothelial barrier permeability and enhances transendothelial migration of malignant breast epithelial cells

Fibrinogen

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