Bone marrow angiogenesis and mast cell density increase simultaneously with progression of human multiple myeloma

Ribatti, Doménico; Vacca, Angelo; Quondamatteo, Fabio; Ria, Roberto; Minischetti, Monica; Marzullo, Andrea; Herken, Rainer; Roncali, Luisa; Dammacco, Franco

doi:10.1038/sj.bjc.6690070

Cited by 236 publications

(149 citation statements)

References 31 publications

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“…The discrepancies in previous studies (Veiga et al, 1998;Hyjek et al, 1999;Ribatti et al, 1999;Vacca et al, 1999b;Arias and Soares, 2000;Ridell and Norrby, 2001) concerning MVD values in reactive lymphoid tissues and lymphomas were the primary issue for this investigation. Our data confirm that both in reactive lymph nodes and in lymph nodes with follicular lymphomas, the MVD is higher in the paracortex than in the follicles and that there is no difference in MVD between reactive germinal centres and neoplastic follicles.…”

Section: Discussionmentioning

confidence: 82%

Vascular patterns in reactive lymphoid tissue and in non-Hodgkin's lymphoma

et al. 2003

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The few studies published on angiogenesis in lymphoma have raised the question of whether or not microvessel density (MVD) is associated with more aggressive disease and have reported the observation that in follicular lymphomas, vessels are mature rather than immature. We investigated MVD and the vascular phenotype within follicular or diffuse large B-cell lymphomas, reactive nodes and tonsils. Vascular phenotype was defined by the expression or loss of reactivity to the antibody LH39 (detecting the LH39 laminin epitope of the basement membrane in mature vessels) and by detection of aVb3 (expressed on immature vessels). In reactive nodes and in follicular lymphomas, MVD was higher in the paracortex than in germinal centres or in neoplastic follicles. However, in neoplastic follicles an increase in aVb3-positive endothelium suggested the activation of an angiogenic pathway different from that present in the reactive follicles. In large B-cell lymphomas, MVD was higher than in reactive and neoplastic follicles but lower than in the reactive paracortex. The number of immature vessels (LH39 negative) and of aVb3-positive vessels was higher than in reactive lymph nodes and follicular lymphoma suggesting that a switch to a different angiogenic pathway has occurred. Finally, we have demonstrated that within reactive and neoplastic follicles vascular regression is occurring, perhaps constraining the growth of reactive follicles alongside other phenomena such as apoptosis. Vascular regression was previously believed to occur in adults only in ovarian and endometrial tissue. We conclude that different types of angiogenesis are present in follicular lymphomas and large B-cell lymphomas. This has implications for possible future therapies.

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Section: Discussionmentioning

confidence: 82%

Vascular patterns in reactive lymphoid tissue and in non-Hodgkin's lymphoma

et al. 2003

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“…8 MC density is highly correlated with the extent of both normal and pathological angiogenesis, such as that in chronic inflammatory diseases and tumors. 9 We have demonstrated that in multiple myeloma and B cell non-Hodgkin's lymphoma there is a striking association between MC and microvessel counts and that both increase in function of tumor progression, as defined by its increasing malignancies grades, 10,11 while in both benign lymphadenopathies and in B cell non-Hodgkin's lymphoma angiogenesis is highly correlated with the total and MC tryptase-positive counts. 12 Tryptase contained in MC secretory granules is angiogenic both in vitro and in vivo experimental models, and specific tryptase inhibitors suppress this activity.…”

Section: Introductionmentioning

confidence: 95%

Correlation of bone marrow angiogenesis and mast cells with tryptase activity in myelodysplastic syndromes

et al. 2002

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Bone marrow samples from 30 patients with myelodysplastic syndromes (MDS) grouped according to the International Prognostic Scoring System for MDS were investigated for counts of microvessels, total metachromatic mast cells (MC) and MC expressing tryptase, an angiogenesis-inducing molecule. Counts were higher in patients with a poor prognosis. The observation of a high correlation between microvessel counts and both total metachromatic and tryptase-reactive MC in all samples suggests that angiogenesis in MDS increases with their progression and that MC may intervene in the angiogenic response in MDS through tryptase contained in their secretory granules.

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“…[1][2][3] These data, together with the known anti-angiogenic properties of thalidomide, 4 provided the rationale for the use of thalidomide in the treatment of patients with MM. 5 Remarkably, thalidomide induced clinical responses in 32% of MM patients whose disease was refractory to conventional and even to high-dose chemotherapy, 5 suggesting that thalidomide can overcome in vivo drug resistance.…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo

et al. 2003

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We have previously shown that thalidomide and its potent immunomodulatory derivatives (IMiDs) inhibit the in vitro growth of multiple myeloma (MM) cell lines and patient MM cells that are resistant to conventional therapy. In this study, we further characterize the effect of these drugs on growth of B cell malignancies and angiogenesis. We established a beigenude-xid (BNX) mouse model to allow for simultaneous in vivo measurement of both anti-tumor and anti-angiogenic effects of thalidomide and its analogs. Daily treatment (50 mg/kg/d) with thalidomide or IMiDs was nontoxic. The IMiDs were significantly more potent than thalidomide in vivo in suppressing tumor growth, evidenced by decreased tumor volume and prolonged survival, as well as mediating anti-angiogenic effects, as determined by decreased microvessel density. Our results therefore show that the IMiDs have more potent direct antitumor and anti-angiogenic effects than thalidomide in vivo, providing the framework for clinical protocols evaluating these agents in MM and other B cell neoplasms.

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Bone marrow angiogenesis and mast cell density increase simultaneously with progression of human multiple myeloma

Cited by 236 publications

References 31 publications

Vascular patterns in reactive lymphoid tissue and in non-Hodgkin's lymphoma

Vascular patterns in reactive lymphoid tissue and in non-Hodgkin's lymphoma

Correlation of bone marrow angiogenesis and mast cells with tryptase activity in myelodysplastic syndromes

Immunomodulatory analogs of thalidomide inhibit growth of Hs Sultan cells and angiogenesis in vivo

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