nach oben

Journal of Cancer Research and Clinical Oncology

Erschienen in:

01.08.2015 | Original Article – Clinical Oncology

Immunohistochemical expression of endoglin offers a reliable estimation of bone marrow neoangiogenesis in multiple myeloma

verfasst von: Michael G. Alexandrakis, Ioannis K. Neonakis, Constantina A. Pappa, Ioannis Konsolas, Maria Kokonozaki, Rodanthi Vyzoukaki, Stella Soundoulounaki, Athina Xekalou, Katerina Sfiridaki, George Tsirakis

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 8/2015

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The aim of the present study was to evaluate CD105 tissue marker in the bone marrow (BM) of multiple myeloma (MM) patients. CD105 was evaluated using immunohistochemical method. An effort was made to correlate this marker with BM microvascular density (MVD) along with other known markers of angiogenesis in order to evaluate its clinical significance.

Methods

BM MVD was estimated by CD31. CD105 in BM was estimated by immunohistochemical method in 54 newly diagnosed patients with MM. Circulating levels of known angiogenic factors such as basic fibroblast growth factor (b-FGF) and soluble CD105 (sCD105) were measured by ELISA in the same group of patients. All these factors were also measured in 20 age- and sex-matched healthy controls.

Results

We found that CD105 MVD, along with the expected CD31 MVD, and serum levels of sCD105 and bFGF were increased, also in parallel with disease stage, and all were decreased after effective treatment. Moreover, CD105 MVD correlated with all the aforementioned markers of angiogenesis.

Conclusions

Our results indicated that CD105 MVD is following the behavior of CD31 MVD in MM, suggesting being a valid marker of BM neoangiogenesis in MM. Its prognostic impact remains to be proven.

Alexandrakis MG, Tsirakis G (2014) Circulating levels of soluble angiogenic factors in multiple myeloma: correlation with parameters of disease activity and prognosis. Curr Angiogenesis. doi:10.2174/22115528113026660012

Alexandrakis MG, Passam FH, Dambaki C, Pappa CA, Stathopoulos EN (2004a) The relation between bone marrow angiogenesis and the proliferation index Ki-67 in multiple myeloma. J Clin Pathol 57(8):856–860PubMedPubMedCentralCrossRef

Alexandrakis MG, Passam FJ, Ganotakis E, Dafnis E, Dambaki C, Konsolas J et al (2004b) Bone marrow microvascular density and angiogenic growth factors in multiple myeloma. Clin Chem Lab Med 42(10):1122–1126PubMedCrossRef

Alexandrakis MG, Passam FH, Pappa CA, Dambaki C, Sfakiotaki G, Alegakis AK et al (2004c) Expression of proliferating cell nuclear antigen (PCNA) in multiple myeloma: its relationship to bone marrow microvessel density and other factors of disease activity. Int J Immunopathol Pharmacol 17(1):49–56PubMed

Bernabeu C, Lopez-Novoa JM, Quintanilla M (2009) The emerging role of TGF-beta superfamily coreceptors in cancer. Biochim Biophys Acta 1792(10):954–973PubMedCrossRef

Bhatti SS, Kumar L, Dinda AK, Dawar R (2006) Prognostic value of bone marrow angiogenesis in multiple myeloma: use of light microscopy as well as computerized image analyzer in the assessment of microvessel density and total vascular area in multiple myeloma and its correlation with various clinical, histological, and laboratory parameters. Am J Hematol 81:649–656PubMedCrossRef

Duff SE, Li C, Garland JM, Kumar S (2003) CD105 is important for angiogenesis: evidence and potential applications. FASEB J 17:984–992PubMedCrossRef

Hatjiharissi E, Terpos E, Papaioannou M, Hatjileontis C, Kaloutsi V, Galaktidou G et al (2004) The combination of intermediate doses of thalidomide and dexamethasone reduces bone marrow micro-vessel density but not serum levels of angiogenic cytokines in patients with refractory/relapsed multiple myeloma. Hematol Oncol 22:159–168PubMedCrossRef

Henry LA, Johnson DA, Sarrio D, Lee S, Quinlan PR, Crook T et al (2011) Endoglin expression in breast tumor cells suppresses invasion and metastasis and correlates with improved clinical outcome. Oncogene 30:1046–1058PubMedCrossRef

Hillengass J, Wasser K, Delorme S, Kiessling F, Zechmann C, Benner A, Kauczor HU, Ho AD, Goldschmidt H, Moehler TM (2007) Lumbar bone marrow microcirculation measurements from dynamic contrast-enhanced magnetic resonance imaging is a predictor of event-free survival in progressive multiple myeloma. Clin Cancer Res 13:475–481PubMedCrossRef

Kumar S, Fonseca R, Dispenzieri A, Lacy MQ, Lust JA, Witzig TE et al (2002) Bone marrow angiogenesis in multiple myeloma: effect of therapy. Br J Haematol 119:665–671PubMedCrossRef

Kumar S, Gertz MA, Dispenzieri A, Lacy MQ, Wellik LA, Fonseca R (2004a) Prognostic value of bone marrow angiogenesis in patients with multiple myeloma undergoing high-dose therapy. Bone Marrow Transplant 34:235–239PubMedCrossRef

Kumar S, Witzig TE, Dispenzieri A, Lacy MQ, Wellik LE, Fonseca R et al (2004b) Effect of thalidomide therapy on bone marrow angiogenesis in multiple myeloma. Leukemia 18:624–627PubMedCrossRef

Lakshman M, Huang X, Ananthanarayanan V, Jovanovic B, Liu Y, Craft CS (2011) Endoglin suppresses human prostate cancer metastasis. Clin Exp Metastasis 28:39–53PubMedPubMedCentralCrossRef

Menzel T, Rahman Z, Calleja E, White K, Wilson EL, Wieder R et al (1996) Elevated intracellular level of basic fibroblast growth factor correlates with stage of chronic lymphocytic leukemia and is associated with resistance to fludarabine. Blood 87:1056–1063PubMed

Moulopoulos LA, Dimopoulos MA, Christoulas D, Kastritis E, Anagnostou D, Koureas A et al (2010) Diffuse MRI marrow pattern correlates with increased angiogenesis, advanced disease features and poor prognosis in newly diagnosed myeloma treated with novel agents. Leukemia 24:1206–1212PubMedCrossRef

Munshi NC, Wilson C (2001) Increased bone marrow microvessel density in newly diagnosed multiple myeloma carries a poor prognosis. Semin Oncol 28:565–569PubMedCrossRef

Nassiri F, Cusimano MD, Scheithauer BW, Rotondo F, Fazio A, Yousef GM et al (2011) Endoglin (CD105): a review of its role in angiogenesis and tumor diagnosis, progression and therapy. Anticancer Res 31:2283–2290PubMed

Otjacques E, Binsfeld M, Noel A, Beguin Y, Cataldo D, Caers J (2011) Biological aspects of angiogenesis in multiple myeloma. Int J Hematol 94:505–518PubMedCrossRef

Pappa C, Alexandrakis M, Boula A, Psarakis F, Kolovou A, Bantouna V et al (2013) Emerging roles of endoglin/CD105 and angiogenic cytokines for disease development and progression in multiple myeloma patients. Hematol Oncol. doi:10.1002/hon.2044

Pruneri G, Ponzoni M, Ferreri AJ, Decarli N, Tresoldi M, Raggi F et al (2002) Microvessel density, a surrogate marker of angiogenesis, is significantly related to survival in multiple myeloma patients. Br J Haematol 118:817–820PubMedCrossRef

Rajkumar SV, Mesa RA, Fonseca R, Schroeder G, Plevak MF, Dispenzieri A et al (2002) Bone marrow angiogenesis in 400 patients with monoclonal gammopathy of undetermined significance, multiple myeloma, and primary amyloidosis. Clin Cancer Res 8:2210–2216PubMed

Santibanez JF, Letamendia A, Perez-Barriocanal F, Silvestri C, Saura M, Vary CP et al (2007) Endoglin increases eNOS expression by modulating Smad2 protein levels and Smad2-dependent TGF-beta signaling. J Cell Physiol 210:456–468PubMedCrossRef

Sezer O, Niemöller K, Jakob C, Zavrski I, Heider U, Eucker J et al (2001a) Relationship between bone marrow angiogenesis and plasma cell infiltration and serum beta2-microglobulin levels in patients with multiple myeloma. Ann Hematol 80:598–601PubMedCrossRef

Sezer O, Niemöller K, Kaufmann O, Eucker J, Jakob C, Zavrski I et al (2001b) Decrease of bone marrow angiogenesis in myeloma patients achieving a remission after chemotherapy. Eur J Haematol 66:238–244PubMedCrossRef

Tsirakis G, Pappa CA, Kanellou P, Stratinaki MA, Xekalou A, Psarakis FE et al (2012a) Role of platelet-derived growth factor-AB in tumour growth and angiogenesis in relation with other angiogenic cytokines in multiple myeloma. Hematol Oncol 30:131–136PubMedCrossRef

Tsirakis G, Pappa CA, Spanoudakis M, Chochlakis D, Alegakis A, Psarakis FE et al (2012b) Clinical significance of sCD105 in angiogenesis and disease activity in multiple myeloma. Eur J Intern Med 23:368–373PubMedCrossRef

Vacca A, Ribatti D, Roncali L, Ranieri G, Serio G, Silvestris F et al (1994) marrow angiogenesis and progression in multiple myeloma. Br J Haematol 87:503–508PubMedCrossRef

Wong VC, Chan PL, Bernabeu C, Law S, Wang LD, Li JL et al (2008) Identification of an invasion and tumor-suppressing gene, Endoglin (ENG), silenced by both epigenetic inactivation and allelic loss in esophageal squamous cell carcinoma. Int J Cancer 123:2816–2823PubMedCrossRef

Zheng W, Liu D, Fan X, Powers L, Goswami M, Hu Y et al (2013) Potential therapeutic biomarkers in plasma cell myeloma: a flow cytometry study. Cytom B Clin Cytom 84:222–228CrossRef

Titel: Immunohistochemical expression of endoglin offers a reliable estimation of bone marrow neoangiogenesis in multiple myeloma
verfasst von: Michael G. Alexandrakis
Ioannis K. Neonakis
Constantina A. Pappa
Ioannis Konsolas
Maria Kokonozaki
Rodanthi Vyzoukaki
Stella Soundoulounaki
Athina Xekalou
Katerina Sfiridaki
George Tsirakis
Publikationsdatum: 01.08.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 8/2015
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-015-1952-z

Springer Medizin

Immunohistochemical expression of endoglin offers a reliable estimation of bone marrow neoangiogenesis in multiple myeloma