Skip to main content
Erschienen in: Clinical & Experimental Metastasis 2/2017

25.01.2017 | Research Paper

Activated thrombin-activatable fibrinolysis inhibitor attenuates the angiogenic potential of endothelial cells: potential relevance to the breast tumour microenvironment

verfasst von: Zainab A. Bazzi, Jennifer Balun, Dora Cavallo-Medved, Lisa A. Porter, Michael B. Boffa

Erschienen in: Clinical & Experimental Metastasis | Ausgabe 2/2017

Einloggen, um Zugang zu erhalten

Abstract

Thrombin-activatable fibrinolysis inhibitor (TAFI) is a basic carboxypeptidase zymogen present in blood plasma. Proteolytic activation of TAFI by thrombin, thrombin in complex with the endothelial cell cofactor thrombomodulin, or plasmin results in an enzyme (TAFIa) that removes carboxyl-terminal lysine residues from protein and peptide substrates, including cell-surface plasminogen receptors. TAFIa is therefore capable of inhibiting plasminogen activation in the pericellular milieu. Since plasminogen activation has been linked to angiogenesis, TAFIa could therefore have anti-angiogenic properties, and indeed TAFIa has been shown to inhibit endothelial tube formation in a fibrin matrix. In this study, the TAFI pathway was manipulated by providing exogenous TAFI or TAFIa or by adding a potent and specific inhibitor of TAFIa. We found that TAFIa elicited a series of anti-angiogenic responses by endothelial cells, including decreased endothelial cell proliferation, cell invasion, cell migration, tube formation, and collagen degradation. Moreover, TAFIa decreased tube formation and proteolysis in endothelial cell culture grown alone and in co-culture with breast cancer cell lines. In accordance with these findings, inhibition of TAFIa increased secretion of matrix metalloprotease proenzymes by endothelial and breast cancer cells. Finally, treatment of endothelial cells with TAFIa significantly inhibited plasminogen activation. Taken together our results suggest a novel role for TAFI in inhibiting tumour angiogenic behaviors in breast cancer.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
4.
Zurück zum Zitat Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1(1):27–31CrossRefPubMed Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1(1):27–31CrossRefPubMed
6.
9.
Zurück zum Zitat Oh CW, Hoover-Plow J, Plow EF (2003) The role of plasminogen in angiogenesis in vivo. J Thromb Haemost 1(8):1683–1687CrossRefPubMed Oh CW, Hoover-Plow J, Plow EF (2003) The role of plasminogen in angiogenesis in vivo. J Thromb Haemost 1(8):1683–1687CrossRefPubMed
12.
Zurück zum Zitat Ceruti P, Principe M, Capello M, Cappello P, Novelli F (2013) Three are better than one: plasminogen receptors as cancer theranostic targets. Exp Hematol Oncol 2(1):1–11. doi:10.1186/2162-3619-2-12 CrossRef Ceruti P, Principe M, Capello M, Cappello P, Novelli F (2013) Three are better than one: plasminogen receptors as cancer theranostic targets. Exp Hematol Oncol 2(1):1–11. doi:10.​1186/​2162-3619-2-12 CrossRef
13.
Zurück zum Zitat Pepper MS (2001) Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis. Arterioscler Thromb Vasc Biol 21(7):1104–1117CrossRefPubMed Pepper MS (2001) Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis. Arterioscler Thromb Vasc Biol 21(7):1104–1117CrossRefPubMed
14.
Zurück zum Zitat Rakic JM, Maillard C, Jost M, Bajou K, Masson V, Devy L, Lambert V, Foidart JM, Noel A (2003) Role of plasminogen activator-plasmin system in tumor angiogenesis. Cell Mol Life Sci 60(3):463–473CrossRefPubMed Rakic JM, Maillard C, Jost M, Bajou K, Masson V, Devy L, Lambert V, Foidart JM, Noel A (2003) Role of plasminogen activator-plasmin system in tumor angiogenesis. Cell Mol Life Sci 60(3):463–473CrossRefPubMed
15.
17.
Zurück zum Zitat Bazzi ZA, Lanoue D, El-Youssef M, Romagnuolo R, Tubman J, Cavallo-Medved D, Porter LA, Boffa MB (2016) Activated thrombin-activatable fibrinolysis inhibitor (TAFIa) attenuates breast cancer cell metastatic behaviors through inhibition of plasminogen activation and extracellular proteolysis. BMC Cancer 16(1):328. doi:10.1186/s12885-016-2359-1 CrossRefPubMedPubMedCentral Bazzi ZA, Lanoue D, El-Youssef M, Romagnuolo R, Tubman J, Cavallo-Medved D, Porter LA, Boffa MB (2016) Activated thrombin-activatable fibrinolysis inhibitor (TAFIa) attenuates breast cancer cell metastatic behaviors through inhibition of plasminogen activation and extracellular proteolysis. BMC Cancer 16(1):328. doi:10.​1186/​s12885-016-2359-1 CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Higuchi T, Nakamura T, Kakutani H, Ishi H (2009) Thrombomodulin suppresses invasiveness of HT1080 tumor cells by reducing plasminogen activation on the cell surface through activation of thrombin-activatable fibrinolysis inhibitor. Biol Pharm Bull 32(2):179–185CrossRefPubMed Higuchi T, Nakamura T, Kakutani H, Ishi H (2009) Thrombomodulin suppresses invasiveness of HT1080 tumor cells by reducing plasminogen activation on the cell surface through activation of thrombin-activatable fibrinolysis inhibitor. Biol Pharm Bull 32(2):179–185CrossRefPubMed
20.
21.
Zurück zum Zitat Guimaraes AHC, Laurens N, Weijers EM, Koolwijk P, van Hinsbergh VWM, Rijken DC (2007) TAFI and pancreatic carboxypeptidase B modulate in vitro capillary tube formation by human microvascular endothelial cells. Arterioscl Throm Vas 27 (10):2157–2162. doi:10.1161/Atvbaha.107.150144 CrossRef Guimaraes AHC, Laurens N, Weijers EM, Koolwijk P, van Hinsbergh VWM, Rijken DC (2007) TAFI and pancreatic carboxypeptidase B modulate in vitro capillary tube formation by human microvascular endothelial cells. Arterioscl Throm Vas 27 (10):2157–2162. doi:10.​1161/​Atvbaha.​107.​150144 CrossRef
23.
Zurück zum Zitat Grant DS, Lelkes PL, Fukuda K, Kleinman HK (1991) Intracellular mechanisms involved in basement-membrane induced blood-vessel differentiation invitro. In Vitro Cell Dev B 27 (4):327–336CrossRef Grant DS, Lelkes PL, Fukuda K, Kleinman HK (1991) Intracellular mechanisms involved in basement-membrane induced blood-vessel differentiation invitro. In Vitro Cell Dev B 27 (4):327–336CrossRef
24.
Zurück zum Zitat Kubota Y, Kleinman HK, Martin GR, Lawley TJ (1988) Role of laminin and basement-membrane in the morphological-differentiation of human-endothelial cells into capillary-like structures. J Cell Biol 107(4):1589–1598. DOI:10.1083/jcb.107.4.1589 CrossRefPubMed Kubota Y, Kleinman HK, Martin GR, Lawley TJ (1988) Role of laminin and basement-membrane in the morphological-differentiation of human-endothelial cells into capillary-like structures. J Cell Biol 107(4):1589–1598. DOI:10.​1083/​jcb.​107.​4.​1589 CrossRefPubMed
25.
Zurück zum Zitat Sameni M, Dosescu J, Moin K, Sloane BF (2003) Functional imaging of proteolysis: stromal and inflammatory cells increase tumor proteolysis. Mol Imaging 2(3):159–175CrossRefPubMed Sameni M, Dosescu J, Moin K, Sloane BF (2003) Functional imaging of proteolysis: stromal and inflammatory cells increase tumor proteolysis. Mol Imaging 2(3):159–175CrossRefPubMed
27.
Zurück zum Zitat Sameni M, Cavallo-Medved D, Dosescu J, Jedeszko C, Moin K, Mullins SR, Olive MB, Rudy D, Sloane BF (2009) Imaging and quantifying the dynamics of tumor-associated proteolysis. Clin Exp Metastasis 26(4):299–309. doi:10.1007/s10585-008-9218-7 CrossRefPubMed Sameni M, Cavallo-Medved D, Dosescu J, Jedeszko C, Moin K, Mullins SR, Olive MB, Rudy D, Sloane BF (2009) Imaging and quantifying the dynamics of tumor-associated proteolysis. Clin Exp Metastasis 26(4):299–309. doi:10.​1007/​s10585-008-9218-7 CrossRefPubMed
28.
30.
Zurück zum Zitat Mohamed MM, Cavallo-Medved D, Rudy D, Anbalagan A, Moin K, Sloane BF (2010) Interleukin-6 increases expression and secretion of cathepsin B by breast tumor-associated monocytes. Cell Physiol Biochem 25(2–3):315–324. doi:10.1159/000276564 CrossRefPubMedPubMedCentral Mohamed MM, Cavallo-Medved D, Rudy D, Anbalagan A, Moin K, Sloane BF (2010) Interleukin-6 increases expression and secretion of cathepsin B by breast tumor-associated monocytes. Cell Physiol Biochem 25(2–3):315–324. doi:10.​1159/​000276564 CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86(3):353–364CrossRefPubMed Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86(3):353–364CrossRefPubMed
34.
Zurück zum Zitat Ulisse S, Baldini E, Sorrenti S, D’Armiento M (2009) The urokinase plasminogen activator system: a target for anti-cancer therapy. Curr Cancer Drug Targets 9(1):32–71CrossRefPubMed Ulisse S, Baldini E, Sorrenti S, D’Armiento M (2009) The urokinase plasminogen activator system: a target for anti-cancer therapy. Curr Cancer Drug Targets 9(1):32–71CrossRefPubMed
35.
Zurück zum Zitat Pepper MS, Vassalli JD, Montesano R, Orci L (1987) Urokinase-type plasminogen activator is induced in migrating capillary endothelial cells. J Cell Biol 105(6 Pt 1):2535–2541CrossRefPubMed Pepper MS, Vassalli JD, Montesano R, Orci L (1987) Urokinase-type plasminogen activator is induced in migrating capillary endothelial cells. J Cell Biol 105(6 Pt 1):2535–2541CrossRefPubMed
36.
Zurück zum Zitat Pepper MS, Montesano R, Orci L, Vassalli JD (1991) Plasminogen activator inhibitor-1 is induced in microvascular endothelial cells by a chondrocyte-derived transforming growth factor-beta. Biochem Biophys Res Commun 176(2):633–638CrossRefPubMed Pepper MS, Montesano R, Orci L, Vassalli JD (1991) Plasminogen activator inhibitor-1 is induced in microvascular endothelial cells by a chondrocyte-derived transforming growth factor-beta. Biochem Biophys Res Commun 176(2):633–638CrossRefPubMed
42.
Zurück zum Zitat Itoh T, Tanioka M, Yoshida H, Yoshioka T, Nishimoto H, Itohara S (1998) Reduced angiogenesis and tumor progression in gelatinase A-deficient mice. Cancer Res 58(5):1048–1051PubMed Itoh T, Tanioka M, Yoshida H, Yoshioka T, Nishimoto H, Itohara S (1998) Reduced angiogenesis and tumor progression in gelatinase A-deficient mice. Cancer Res 58(5):1048–1051PubMed
44.
Zurück zum Zitat Hollborn M, Stathopoulos C, Steffen A, Wiedemann P, Kohen L, Bringmann A (2007) Positive feedback regulation between MMP-9 and VEGF in human RPE cells. Invest Ophthalmol Vis Sci 48(9):4360–4367. doi:10.1167/iovs.06-1234 CrossRefPubMed Hollborn M, Stathopoulos C, Steffen A, Wiedemann P, Kohen L, Bringmann A (2007) Positive feedback regulation between MMP-9 and VEGF in human RPE cells. Invest Ophthalmol Vis Sci 48(9):4360–4367. doi:10.​1167/​iovs.​06-1234 CrossRefPubMed
53.
Zurück zum Zitat Everts V, van der Zee E, Creemers L, Beertsen W (1996) Phagocytosis and intracellular digestion of collagen, its role in turnover and remodelling. Histochem J 28(4):229–245CrossRefPubMed Everts V, van der Zee E, Creemers L, Beertsen W (1996) Phagocytosis and intracellular digestion of collagen, its role in turnover and remodelling. Histochem J 28(4):229–245CrossRefPubMed
54.
Zurück zum Zitat Grove AD, Prabhu VV, Young BL, Lee FC, Kulpa V, Munson PJ, Kohn EC (2002) Both protein activation and gene expression are involved in early vascular tube formation in vitro. Clin Cancer Res 8(9):3019–3026PubMed Grove AD, Prabhu VV, Young BL, Lee FC, Kulpa V, Munson PJ, Kohn EC (2002) Both protein activation and gene expression are involved in early vascular tube formation in vitro. Clin Cancer Res 8(9):3019–3026PubMed
55.
Zurück zum Zitat Schnaper HW, Barnathan ES, Mazar A, Maheshwari S, Ellis S, Cortez SL, Baricos WH, Kleinman HK (1995) Plasminogen activators augment endothelial cell organization in vitro by two distinct pathways. J Cell Physiol 165(1):107–118. doi:10.1002/jcp.1041650114 CrossRefPubMed Schnaper HW, Barnathan ES, Mazar A, Maheshwari S, Ellis S, Cortez SL, Baricos WH, Kleinman HK (1995) Plasminogen activators augment endothelial cell organization in vitro by two distinct pathways. J Cell Physiol 165(1):107–118. doi:10.​1002/​jcp.​1041650114 CrossRefPubMed
57.
Zurück zum Zitat Wu C, Kim PY, Swystun LL, Liaw PC, Weitz JI (2016) Activation of protein C and thrombin activable fibrinolysis inhibitor on cultured human endothelial cells. J Thromb Haemost 14(2):366–374. doi:10.1111/jth.13222 CrossRefPubMed Wu C, Kim PY, Swystun LL, Liaw PC, Weitz JI (2016) Activation of protein C and thrombin activable fibrinolysis inhibitor on cultured human endothelial cells. J Thromb Haemost 14(2):366–374. doi:10.​1111/​jth.​13222 CrossRefPubMed
58.
Zurück zum Zitat Kim SJ, Shiba E, Ishii H, Inoue T, Taguchi T, Tanji Y, Kimoto Y, Izukura M, Takai S (1997) Thrombomodulin is a new biological and prognostic marker for breast cancer: an immunohistochemical study. Anticancer Res 17(3c):2319–2323PubMed Kim SJ, Shiba E, Ishii H, Inoue T, Taguchi T, Tanji Y, Kimoto Y, Izukura M, Takai S (1997) Thrombomodulin is a new biological and prognostic marker for breast cancer: an immunohistochemical study. Anticancer Res 17(3c):2319–2323PubMed
Metadaten
Titel
Activated thrombin-activatable fibrinolysis inhibitor attenuates the angiogenic potential of endothelial cells: potential relevance to the breast tumour microenvironment
verfasst von
Zainab A. Bazzi
Jennifer Balun
Dora Cavallo-Medved
Lisa A. Porter
Michael B. Boffa
Publikationsdatum
25.01.2017
Verlag
Springer Netherlands
Erschienen in
Clinical & Experimental Metastasis / Ausgabe 2/2017
Print ISSN: 0262-0898
Elektronische ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-017-9837-y

Weitere Artikel der Ausgabe 2/2017

Clinical & Experimental Metastasis 2/2017 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.