Reference(s)
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Cancer type: Multiple Myeloma


HGF/SF expression

Reference Number: 160
Borset, M., Hjorth-Hansen, H., Seidel, C., Sundan, A. & Waage, A. Hepatocyte growth factor and its receptor c-met in multiple myeloma. Blood 88, 3998-4004 (1996).
PubMed link      E-mail link

Reference Number: 161
Borset, M., Seidel, C., Hjorth-Hansen, H., Waage, A. & Sundan, A. The role of hepatocyte growth factor and its receptor c-Met in multiple myeloma and other blood malignancies. Leuk Lymphoma 32, 249-56 (1999).
PubMed link      E-mail link

Reference Number: 162
Derksen, P. W. et al. The hepatocyte growth factor/Met pathway controls proliferation and apoptosis in multiple myeloma. Leukemia 17, 764-74. (2003).
PubMed link      E-mail link

Reference Number: 163
Seidel, C., Borset, M., Hjorth-Hansen, H., Sundan, A. & Waage, A. Role of hepatocyte growth factor and its receptor c-met in multiple myeloma. Med Oncol 15, 145-53 (1998).
PubMed link      E-mail link

Reference Number: 164
Seidel, C. et al. Hepatocyte growth factor in myeloma patients treated with high-dose chemotherapy. Br J Haematol 119, 672-6 (2002).
PubMed link      E-mail link

Reference Number: 165
Turesson, I. et al. Prognostic evaluation in multiple myeloma: an analysis of the impact of new prognostic factors. Br J Haematol 106, 1005-12 (1999).
PubMed link      E-mail link

Reference Number: 166
Seidel, C. et al. Elevated serum concentrations of hepatocyte growth factor in patients with multiple myeloma. The Nordic Myeloma Study Group. Blood 91, 806-12 (1998).
PubMed link      E-mail link

Reference Number: 266
Alexandrakis MG, Passam FH, Sfiridaki A, Kandidaki E, Roussou P, Kyriakou DS. Elevated serum concentration of hepatocyte growth factor in patients with multiple myeloma: correlation with markers of disease activity. Am J Hematol 72:229-33 (2003).
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Reference Number: 267
Urba ska-Rys H, Wierzbowska A, Robak T. Circulating angiogenic cytokines in multiple myeloma and related disorders. Eur Cytokine Netw 14:40-51 (2003).
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Reference Number: 268
Hsiao LT, Lin JT, Yu IT, Chiou TJ, Liu JH, Yen CC, Wang WS, Chen PM. High serum hepatocyte growth factor level in patients with non-Hodgkin's lymphoma. Eur J Maematol 70:282-9 (2003).
PubMed link      E-mail link

Reference Number: 302
Tjin EP, Derksen PW, Kataoka H, Spaargaren M, Pals ST. Multiple myeloma cells catalyze hepatocyte growth factor (HGF) activation by secreting the serine protease HGF-activator. Blood 104, 2172-5 (2004)
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Reference Number: 303
Vande Broek I, Asosingh K, Allegaert V, Leleu X, Facon T, Vanderkerken K, Van Camp B, Van Riet I. Bone marrow endothelial cells increase the invasiveness of human multiple myeloma cells through upregulation of MMP-9: evidence for a role of hepatocyte growth factor. Leukemia 18, 976-82 (2004)
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Reference Number: 429
Tjin EP, Groen RW, Vogelzang I, Derksen PW, Klok MD, Meijer HP, van Eeden S, Pals ST, Spaargaren M. Functional analysis of HGF/MET signaling and aberrant HGF-activator expression in diffuse large B-cell lymphoma. Blood107, 760-8 (2006)
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Reference Number: 430
Holt RU, Baykov V, Ro TB, Brabrand S, Waage A, Sundan A, Borset M. Human myeloma cells adhere to fibronectin in response to hepatocyte growth factor. Haematologica. 90, 436 (2005)
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Reference Number: 432
Andersen NF, Standal T, Nielsen JL, Heickendorff L, Borset M, Sorensen FB, Abildgaard N. Syndecan-1 and angiogenic cytokines in multiple myeloma: correlation with bone marrow angiogenesis and survival. Br J Haematol. 128, 210-7 (2005)
PubMed link      E-mail link

Reference Number: 514
Standal T, Abildgaard N, Fagerli UM, Stordal B, Hjertner O, Borset M, Sundan A. HGF inhibits BMP-induced osteoblastogenesis: possible implications for the bone disease of multiple myeloma. Blood. 109, 3024-30 (2007)
PubMed link      E-mail link

Reference Number: 515
Kara IO, Sahin B, Gunesacar R, Unsal C. Clinical significance of hepatocyte growth factor, platelet-derived growth factor-AB, and transforming growth factor-alpha in bone marrow and peripheral blood of patients with multiple myeloma. Adv Ther. 23, 635-45 (2006)
PubMed link      E-mail link

Reference Number: 552
Alexandrakis MG, Sfiridaki A, Miyakis S, Pappa C, Kandidaki E, Alegakis A, Margioris AN. Relationship between serum levels of vascular endothelial growth factor, hepatocyte growth factor and matrix metalloproteinase-9 with biochemical markers of bone disease in multiple myeloma. Clin Chim Acta. 379, 31-5 (2007)
PubMed link      E-mail link

Reference Number: 810
Pour L, Svachova H, Adam Z, Mikulkova Z, Buresova L, Kovarova L, Buchler T, Penka M, Vorlicek J, Hajek R. Pretreatment hepatocyte growth factor and thrombospondin-1 levels predict response to high-dose chemotherapy for multiple myeloma. Neoplasma. 57, 29-34 (2010)
PubMed link      E-mail link

Reference Number: 812
Wader KF, Fagerli UM, Holt RU, Stordal B, Børset M, Sundan A, Waage A. Elevated serum concentrations of activated hepatocyte growth factor activator in patients with multiple myeloma. Eur J Haematol. 81, 380-3 (2008)
PubMed link      E-mail link

Reference Number: 813
Zdzisinska B, Bojarska-Junak A, Dmoszynska A, Kandefer-Szerszen M. Abnormal cytokine production by bone marrow stromal cells of multiple myeloma patients in response to RPMI8226 myeloma cells. Arch Immunol Ther Exp (Warsz). 56, 207-21 (2008)
PubMed link      E-mail link

Reference Number: 997
Purdue MP, Lan Q, Menashe I, Zheng T, Zhang Y, Yeager M, Hosgood HD 3rd, Zahm SH, Chanock SJ, Rothman N, Baris D. Variation in innate immunity genes and risk of multiple myeloma. Hematol Oncol. 29, 42-6 (2011)
PubMed link      E-mail link

Reference Number: 1036
Akkök CA, Hervig T, Stamnesfet S, Nesthus I, Melve GK, Lassalle P, Bruserud O. Effects of peripheral blood stem cell apheresis on systemic cytokine levels in patients with multiple myeloma. Cytotherapy. 13, 1259-68 (2011)
PubMed link      E-mail link

Reference Number: 1286
Bonanno G, Mariotti A, Procoli A, Folgiero V, Natale D, De Rosa L, Majolino I, Novarese L, Rocci A, Gambella M, Ciciarello M, Scambia G, Palumbo A, Locatelli F, De Cristofaro R, Rutella S. Indoleamine 2,3-dioxygenase 1 (IDO1) activity correlates with immune system abnormalities in multiple myeloma. J Transl Med. 10, 247 (2012)
PubMed link      E-mail link

Reference Number: 1299
Tsirakis G, Pappa CA, Psarakis FE, Fragioudaki M, Tsioutis C, Stavroulaki E, Boula A, Alexandrakis MG. Serum concentrations and clinical significance of soluble CD40 ligand in patients with multiple myeloma. Med Oncol. 29, 2396-401 (2012)
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Reference Number: 1304
Tsirakis G, Pappa CA, Kaparou M, Boula A, Katsomitrou V, Xekalou A, Kyriakaki S, Alexandrakis MG. The relationship between soluble receptor of interleukin-6 with angiogenic cytokines and proliferation markers in multiple myeloma. Tumour Biol. 34, 859-64 (2013)
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Reference Number: 1330
Kristensen IB, Christensen JH, Lyng MB, Møller MB, Pedersen L, Rasmussen LM, Ditzel HJ, Abildgaard N. Hepatocyte growth factor pathway upregulation in the bone marrow microenvironment in multiple myeloma is associated with lytic bone disease. Br J Haematol. 161, 373-82 (2013)
PubMed link      E-mail link

Reference Number: 1533
Phillip CJ, Zaman S, Shentu S, Balakrishnan K, Zhang J, Baladandayuthapani V, Taverna P, Redkar S, Wang M, Stellrecht CM, Gandhi V. Targeting MET kinase with the small-molecule inhibitor amuvatinib induces cytotoxicity in primary myeloma cells and cell lines. J Hematol Oncol. 6, 92 (2013)
PubMed link      E-mail link

Reference Number: 1653
Ferrucci A, Moschetta M, Frassanito MA, Berardi S, Catacchio I, Ria R, Racanelli V, Caivano A, Solimando AG, Vergara D, Maffia M, Latorre D, Rizzello A, Zito A, Ditonno P, Maiorano E, Ribatti D, Vacca A. A HGF/cMET autocrine loop is operative in multiple myeloma bone marrow endothelial cells and may represent a novel therapeutic target. Clin Cancer Res. 20, 5796-807 (2014)
PubMed link      E-mail link

Reference Number: 1790
Andersen NF, Kristensen IB, Preiss BS, Christensen JH, Abildgaard N Upregulation of Syndecan-1 in the bone marrow microenvironment in multiple myeloma is associated with angiogenesis. Eur J Haematol. 95, 211-7 (2015)
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Reference Number: 1791
Abraham J, Desport E, Rigaud C, Marin B, Bender S, Lacombe C, Moreau S, Yagoubi F, Bordessoule D, Lavergne D, Bridoux F, Jaccard A Hepatocyte growth factor measurement in AL amyloidosis. Amyloid. 22, 112-6 (2015)
PubMed link      E-mail link

Met expression

Reference Number: 160
Borset, M., Hjorth-Hansen, H., Seidel, C., Sundan, A. & Waage, A. Hepatocyte growth factor and its receptor c-met in multiple myeloma. Blood 88, 3998-4004 (1996).
PubMed link      E-mail link

Reference Number: 161
Borset, M., Seidel, C., Hjorth-Hansen, H., Waage, A. & Sundan, A. The role of hepatocyte growth factor and its receptor c-Met in multiple myeloma and other blood malignancies. Leuk Lymphoma 32, 249-56 (1999).
PubMed link      E-mail link

Reference Number: 162
Derksen, P. W. et al. The hepatocyte growth factor/Met pathway controls proliferation and apoptosis in multiple myeloma. Leukemia 17, 764-74. (2003).
PubMed link      E-mail link

Reference Number: 163
Seidel, C., Borset, M., Hjorth-Hansen, H., Sundan, A. & Waage, A. Role of hepatocyte growth factor and its receptor c-met in multiple myeloma. Med Oncol 15, 145-53 (1998).
PubMed link      E-mail link

Reference Number: 448
Stellrecht CM, Phillip CJ, Cervantes-Gomez F, Gandhi V. Multiple myeloma cell killing by depletion of the MET receptor tyrosine kinase. Cancer Res. 67, 9913-20 (2007)
PubMed link      E-mail link

Reference Number: 811
Hov H, Tian E, Holien T, Holt RU, Våtsveen TK, Fagerli UM, Waage A, Børset M, Sundan A. c-Met signaling promotes IL-6-induced myeloma cell proliferation. Eur J Haematol. 82, 277-87 (2009)
PubMed link      E-mail link

Reference Number: 1118
Wader KF, Fagerli UM, Holt RU, Børset M, Sundan A, Waage A. Soluble c-Met in serum of patients with multiple myeloma: correlation with clinical parameters. Eur J Haematol. 87, 394-9 (2011)
PubMed link      E-mail link

Reference Number: 1138
Wader KF, Fagerli UM, Børset M, Lydersen S, Hov H, Sundan A, Bofin A, Waage A. Immunohistochemical analysis of hepatocyte growth factor and c-Met in plasma cell disease. Histopathology. 60, 443-51 (2012)
PubMed link      E-mail link

Reference Number: 1156
Que W, Chen J, Chuang M, Jiang D. Knockdown of c-Met enhances sensitivity to bortezomib in human multiple myeloma U266 cells via inhibiting Akt/mTOR activity. APMIS. 120, 195-203 (2012)
PubMed link      E-mail link

Reference Number: 1330
Kristensen IB, Christensen JH, Lyng MB, Møller MB, Pedersen L, Rasmussen LM, Ditzel HJ, Abildgaard N. Hepatocyte growth factor pathway upregulation in the bone marrow microenvironment in multiple myeloma is associated with lytic bone disease. Br J Haematol. 161, 373-82 (2013)
PubMed link      E-mail link

Reference Number: 1421
Rocci A1, Gambella M, Aschero S, Baldi I, Trusolino L, Cavallo F, Gay F, Larocca A, Magarotto V, Omedè P, Isaia G, Bertotti A, Liberati AM, Catalano L, De Rosa L, Musto P, Vallone R, Falcone A, Drandi D, Ladetto M, Comoglio PM, Boccadoro M, Palumbo A. MET dysregulation is a hallmark of aggressive disease in multiple myeloma patients. Br J Haematol. 164, 841-50 (2014)
PubMed link      E-mail link

Reference Number: 1430
Moschetta M1, Basile A, Ferrucci A, Frassanito MA, Rao L, Ria R, Solimando AG, Giuliani N, Boccarelli A, Fumarola F, Coluccia M, Rossini B, Ruggieri S, Nico B, Maiorano E, Ribatti D, Roccaro AM, Vacca A. Novel targeting of phospho-cMET overcomes drug resistance and induces antitumor activity in multiple myeloma. Clin Cancer Res. 19, 4371-82 (2013)
PubMed link      E-mail link

Reference Number: 1533
Phillip CJ, Zaman S, Shentu S, Balakrishnan K, Zhang J, Baladandayuthapani V, Taverna P, Redkar S, Wang M, Stellrecht CM, Gandhi V. Targeting MET kinase with the small-molecule inhibitor amuvatinib induces cytotoxicity in primary myeloma cells and cell lines. J Hematol Oncol. 6, 92 (2013)
PubMed link      E-mail link

Reference Number: 1653
Ferrucci A, Moschetta M, Frassanito MA, Berardi S, Catacchio I, Ria R, Racanelli V, Caivano A, Solimando AG, Vergara D, Maffia M, Latorre D, Rizzello A, Zito A, Ditonno P, Maiorano E, Ribatti D, Vacca A. A HGF/cMET autocrine loop is operative in multiple myeloma bone marrow endothelial cells and may represent a novel therapeutic target. Clin Cancer Res. 20, 5796-807 (2014)
PubMed link      E-mail link

Poor Prognosis

Reference Number: 163
Seidel, C., Borset, M., Hjorth-Hansen, H., Sundan, A. & Waage, A. Role of hepatocyte growth factor and its receptor c-met in multiple myeloma. Med Oncol 15, 145-53 (1998).
PubMed link      E-mail link

Reference Number: 164
Seidel, C. et al. Hepatocyte growth factor in myeloma patients treated with high-dose chemotherapy. Br J Haematol 119, 672-6 (2002).
PubMed link      E-mail link

Reference Number: 165
Turesson, I. et al. Prognostic evaluation in multiple myeloma: an analysis of the impact of new prognostic factors. Br J Haematol 106, 1005-12 (1999).
PubMed link      E-mail link

Reference Number: 515
Kara IO, Sahin B, Gunesacar R, Unsal C. Clinical significance of hepatocyte growth factor, platelet-derived growth factor-AB, and transforming growth factor-alpha in bone marrow and peripheral blood of patients with multiple myeloma. Adv Ther. 23, 635-45 (2006)
PubMed link      E-mail link

Reference Number: 809
Ludek P, Hana S, Zdenek A, Martina A, Dana K, Tomas B, Lucie K, Marta K, Jaroslav M, Miroslav P, Jiri V, Roman H. Treatment response to bortezomib in multiple myeloma correlates with plasma hepatocyte growth factor concentration and bone marrow thrombospondin concentration. Eur J Haematol. 84, 332-6 (2010)
PubMed link      E-mail link

Reference Number: 810
Pour L, Svachova H, Adam Z, Mikulkova Z, Buresova L, Kovarova L, Buchler T, Penka M, Vorlicek J, Hajek R. Pretreatment hepatocyte growth factor and thrombospondin-1 levels predict response to high-dose chemotherapy for multiple myeloma. Neoplasma. 57, 29-34 (2010)
PubMed link      E-mail link

Mutation of Met

In vitro studies

Reference Number: 162
Derksen, P. W. et al. The hepatocyte growth factor/Met pathway controls proliferation and apoptosis in multiple myeloma. Leukemia 17, 764-74. (2003).
PubMed link      E-mail link

Reference Number: 167
Borset, M. et al. Concomitant expression of hepatocyte growth factor/scatter factor and the receptor c-MET in human myeloma cell lines. J Biol Chem 271, 24655-61 (1996).
PubMed link      E-mail link

Reference Number: 168
Derksen, P. W. et al. Cell surface proteoglycan syndecan-1 mediates hepatocyte growth factor binding and promotes Met signaling in multiple myeloma. Blood 99, 1405-10. (2002).
PubMed link      E-mail link

Reference Number: 169
Hjertner, O. et al. Hepatocyte growth factor (HGF) induces interleukin-11 secretion from osteoblasts: a possible role for HGF in myeloma-associated osteolytic bone disease. Blood 94, 3883-8 (1999).
PubMed link      E-mail link

Reference Number: 170
Seidel, C. et al. High levels of soluble syndecan-1 in myeloma-derived bone marrow: modulation of hepatocyte growth factor activity. Blood 96, 3139-46 (2000).
PubMed link      E-mail link

Reference Number: 448
Stellrecht CM, Phillip CJ, Cervantes-Gomez F, Gandhi V. Multiple myeloma cell killing by depletion of the MET receptor tyrosine kinase. Cancer Res. 67, 9913-20 (2007)
PubMed link      E-mail link

Reference Number: 514
Standal T, Abildgaard N, Fagerli UM, Stordal B, Hjertner O, Borset M, Sundan A. HGF inhibits BMP-induced osteoblastogenesis: possible implications for the bone disease of multiple myeloma. Blood. 109, 3024-30 (2007)
PubMed link      E-mail link

Reference Number: 552
Alexandrakis MG, Sfiridaki A, Miyakis S, Pappa C, Kandidaki E, Alegakis A, Margioris AN. Relationship between serum levels of vascular endothelial growth factor, hepatocyte growth factor and matrix metalloproteinase-9 with biochemical markers of bone disease in multiple myeloma. Clin Chim Acta. 379, 31-5 (2007)
PubMed link      E-mail link

Reference Number: 814
Phillip CJ, Stellrecht CM, Nimmanapalli R, Gandhi V. Targeting MET transcription as a therapeutic strategy in multiple myeloma. Cancer Chemother Pharmacol. 63, 587-97 (2009)
PubMed link      E-mail link

Reference Number: 815
Zlei M, Egert S, Wider D, Ihorst G, Wäsch R, Engelhardt M. Characterization of in vitro growth of multiple myeloma cells. Exp Hematol. 35, 1550-61 (2007)
PubMed link      E-mail link

Reference Number: 956
Que W, Chen J. Knockdown of c-Met inhibits cell proliferation and invasion and increases chemosensitivity to doxorubicin in human multiple myeloma U266 cells in vitro. Mol Med Report. 4,343-9 (2011)
PubMed link      E-mail link

Reference Number: 999
Ramani VC, Yang Y, Ren Y, Nan L, Sanderson RD. Heparanase plays a dual role in driving hepatocyte growth factor (HGF) signaling by enhancing HGF expression and activity. J Biol Chem. 286, 6490-9 (2011)
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Reference Number: 1351
Rø TB1, Holien T, Fagerli UM, Hov H, Misund K, Waage A, Sundan A, Holt RU, Børset M. HGF and IGF-1 synergize with SDF-1a in promoting migration of myeloma cells by cooperative activation of p21-activated kinase. Exp Hematol. 41, 646-55 (2013)
PubMed link      E-mail link

Reference Number: 1479
Kristensen IB, Pedersen L, Rø TB, Christensen JH, Lyng MB, Rasmussen LM, Ditzel HJ, Børset M, Abildgaard N. Decorin is down-regulated in multiple myeloma and MGUS bone marrow plasma and inhibits HGF-induced myeloma plasma cell viability and migration. Eur J Haematol. 91, 196-200 (2013)
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Animal models

Reference Number: 171
Hjorth-Hansen, H. et al. Marked osteoblastopenia and reduced bone formation in a model of multiple myeloma bone disease in severe combined immunodeficiency mice. J Bone Miner Res 14, 256-63. (1999).
PubMed link      E-mail link

Therapeutic Development

Reference Number: 288
Hov H, Holt RU, Ro TB, Fagerli UM, Hjorth-Hansen H, Baykov V, Christensen JG, Waage A, Sundan A, Borset M. A selective c-met inhibitor blocks an autocrine hepatocyte growth factor growth loop in ANBL-6 cells and prevents migration and adhesion of myeloma cells. Clin Cancer Res 10, 6686-94 (2004)
PubMed link      E-mail link

Reference Number: 513
Du W, Hattori Y, Yamada T, Matsumoto K, Nakamura T, Sagawa M, Otsuki T, Niikura T, Nukiwa T, Ikeda Y. NK4, an antagonist of hepatocyte growth factor (HGF), inhibits growth of multiple myeloma cells: molecular targeting of angiogenic growth factor. Blood. 109, 3042-9 (2007)
PubMed link      E-mail link

Reference Number: 809
Ludek P, Hana S, Zdenek A, Martina A, Dana K, Tomas B, Lucie K, Marta K, Jaroslav M, Miroslav P, Jiri V, Roman H. Treatment response to bortezomib in multiple myeloma correlates with plasma hepatocyte growth factor concentration and bone marrow thrombospondin concentration. Eur J Haematol. 84, 332-6 (2010)
PubMed link      E-mail link

Reference Number: 814
Phillip CJ, Stellrecht CM, Nimmanapalli R, Gandhi V. Targeting MET transcription as a therapeutic strategy in multiple myeloma. Cancer Chemother Pharmacol. 63, 587-97 (2009)
PubMed link      E-mail link

Reference Number: 1533
Phillip CJ, Zaman S, Shentu S, Balakrishnan K, Zhang J, Baladandayuthapani V, Taverna P, Redkar S, Wang M, Stellrecht CM, Gandhi V. Targeting MET kinase with the small-molecule inhibitor amuvatinib induces cytotoxicity in primary myeloma cells and cell lines. J Hematol Oncol. 6, 92 (2013)
PubMed link      E-mail link

Reference Number: 1560
Slørdahl TS, Denayer T, Moen SH, Standal T, Børset M, Ververken C, Rø TB. Anti-c-MET Nanobody - a new potential drug in multiple myeloma treatment. Eur J Haematol. 91, 399-410 (2013)
PubMed link      E-mail link

Reference Number: 1587
Patnaik A, Weiss GJ, Papadopoulos KP, Hofmeister CC, Tibes R, Tolcher A, Isaacs R, Jac J, Han M, Payumo FC, Cotreau MM, Ramanathan RK. Phase I ficlatuzumab monotherapy or with erlotinib for refractory advanced solid tumours and multiple myeloma. Br J Cancer. 111, 272-80 (2014)
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Reference Number: 1845
Zaman S, Shentu S, Yang J, He J, Orlowski RZ, Stellrecht CM, Gandhi V. Targeting the pro-survival protein MET with tivantinib (ARQ 197) inhibits growth of multiple myeloma cells. Neoplasia. 17, 289-300 (2015)
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Reviews

Reference Number: 887
Mahtouk K, Tjin EP, Spaargaren M, Pals ST. The HGF/MET pathway as target for the treatment of multiple myeloma and B-cell lymphomas. Biochim Biophys Acta. 1806, 208-19 (2010)
PubMed link      E-mail link

Reference Number: 890
Børset M, Seidel C, Hjorth-Hansen H, Waage A, Sundan A. The role of hepatocyte growth factor and its receptor c-Met in multiple myeloma and other blood malignancies. Leuk Lymphoma. 32, 249-56 (1999)
PubMed link      E-mail link

Reference Number: 1875
Gambella M, Palumbo A, Rocci A. MET/HGF pathway in multiple myeloma: from diagnosis to targeted therapy? Expert Rev Mol Diagn. 15, 881-93 (2015)
PubMed link      E-mail link