Molecular Expression of bone marrow angiogenic factors, cell-cell adhesion molecules and matrix-metallo-proteinase plasma cellular disorders: a molecular panel to investigate disease progression

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Maria Cristina Rapanotti


Multiple Myeloma progression, angiogenic markers, matrix-metalloproteinase, cell-cell-adhesion molecules, MCAM/MUC/ CD146, E-Cadherin


Increasing levels of angiogenesis play an important role in the pathogenesis and progression of multiple myeloma (MM). Malignant plasma cells promote a gradual increase in the degree of angiogenesis, modulation of specific cell-cell adhesion molecules and secretion of matrix-metallo-proteinases (MMPs), changing the BM composition from benign conditions, such as MGUS, to smouldering multiple myeloma (SM) and to active MM. We aimed to identify a gene expression profile, helpful to discriminate the “angiogenic potential” in BM and PB plasma cells from MGUS, SMM and active MM patients analyzed at diagnosis. We analyzed the expression of cell-cell adhesion molecules such as VE-Cadherin, E-Cadherin MCAM/MUC18/CD146 and of the MMP-2 and MMP-9. MCAM/MUC18 expression resulted mostly associated with that of the pivotal angiogenic factors VEGF and Ang2, and in MGUS the pattern was different in steady state, compared to progression towards SM. Furthermore, E-Cadherin, the main epithelial cell-cell-adhesion molecule, unexpectedly resulted overexpressed in MM.




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1. Bartl R. Histologic classification and staging of multiple myeloma. Hematol Oncol. 1988; 6 (2):107-113.
2. Folkman J, Shing Y Angiogenesis. J Biol Chem. 1992; 267(16):10931-10934.
3. Vacca A, Ribatti D, Roccaro AM, Ria R, Palermo L, Dammacco F. Bone marrow angiogenesis and plasma cell angiogenic and invasive potential in patients with active multiple myeloma. Acta Haematol. 2001; 106(4):162-169.
4. Randi AM, Laffan MA, Starke RD. Von Willebrand factor, angiodysplasia and angiogenesis. Mediterr J Hematol Infect Dis. 2013 Sep 2;5(1):e2013060. doi: 10.4084/MJHID.2013.060.
5. Vacca A, Ribatti D, Roccaro AM, Ria R, Palermo L, Dammacco F. Bone marrow angiogenesis and plasma cell angiogenic and invasive potential in patients with active multiple myeloma. Acta Haematol. 2001; 106(4):162-169.
6. Jakob C, Sterz J, Zavrski I., Heider U, Kleeberg L, Fleissner C, Kaiser M, Sezer O. Angiogenesis in multiple myeloma. Eur J Cancer 2006; 42(11):1581-1590.
7. Colla S, Morandi F, Lazzaretti M, Polistena P, Svaldi M, Coser P, Bonomini S, Hojden M, Martella E, Chisesi T, Rizzoli V, Giuliani N.Do human myeloma cells directly produce basic FGF? Blood. 2003; 15;102(8):3071-2; author reply 3072-3.
8. Vande Broek I, Vanderkerken K, Van Camp B, Van Riet I. Extravasation and homing mechanisms in multiple myeloma. Clin Exp Metastasis. 2008;25(4):325-34. Epub 2007 Oct 19.
9. Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003; 6:401-410.
10. Ribatti D, Nico B, Crivellato E, Roccaro AM, Vacca A.The history of the angiogenic switch concept. Leukemia. 2007; 21(1):44-52.
11. Vacca A, Ribatti D, Presta M, Minischetti M, Iurlaro M, Ria R, Albini A, Bussolino F, Dammacco F. Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma. Blood. 1999; 93(9):3064-3073.
12. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, Kumar S, Hillengass J, Kastritis E, Richardson P, Landgren O, Paiva B, Dispenzieri A, Weiss B, LeLeu X, Zweegman S, Lonial S, Rosinol L, Zamagni E, Jagannath S, Sezer O, Kristinsson SY, Caers J, Usmani SZ, Lahuerta JJ, Johnsen HE, Beksac M, Cavo M, Goldschmidt H, Terpos E, Kyle RA, Anderson KC, Durie BG, Miguel JF. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014; 15(12):538-548. doi: 10.1016/S1470-2045(14)70442-5.
13. Marascuilo LA, McSweeney M. Nonparametric post hoc comparisons for trend. Psychol Bull. 1967; 67(6):401-412.
14. Rapanotti MC, Suarez Viguria TM, Costanza G, Ricozzi I., Pierantozzi A, Di Stefani A, Campione E., Bernardini S, Chimenti S, Orlandi A, Bianchi L. (2014) “Sequential molecular analysis of circulating MCAM/MUC18 expression: a disease biomarker related to clinical out come in melanoma”. Arch. Dermatol Res., Aug;306(6):527-537. doi: 10.1007/s00403-014-1473-7. Epub 2014 Jun 7.
15. van Roy F, Berx G. The cell-cell adhesion molecule E-cadherin. Cell Mol Life Sci. 2008;65(23):3756-3788. doi: 10.1007/s00018-008-8281-1.
16. Pe?ina-Slaus N. Cancer Tumor suppressor gene E-cadherin and its role in normal and malignant cells. Cell Int. 2003; 3(1):17
17. Syrigos KN, Harrington KJ, Karayiannakis AJ, Baibas N, Katirtzoglou N, Roussou P. Circulating soluble E-cadherin levels are of prognostic significance in patients with multiple myeloma. Anticancer Res. 2004; 24(3):2027-20.
18. Wrobel T, Mazur G, Wolowiec D, Jazwiec B, Sowinska E, Kuliczkowski K. sVE-cadherin and sCD146 serum levels in patients with multiple myeloma. Clin Lab Haematol. 2006; 28(1):36-39.
19. Vajkoczy P, Farhadi M, Gaumann A, Heidenreich R, Erber R, Wunder A, Tonn JC, Menger MD, Breier G. Microtumor growth initiates angiogenic sprouting with simultaneous expression of VEGF, VEGF receptor-2, and angiopoietin-2. J Clin Invest. 2002; 109(6):777-785.
20. Joshi S. Khan R, Sharma M, Kumar L, Sharma A. Angiopoietin-2: a potential novel diagnostic marker in multiple myeloma. Clin Biochem. 2011; 44(8-9):590-595. doi: 10.1016/j.clinbiochem