Angiogenesis in acute promyelocytic leukemia: induction by vascular endothelial growth factor and inhibition by all-trans retinoic acid

Kini, Ameet R.; Peterson, LoAnn; Tallman, Martin S.; Lingen, Mark W.

doi:10.1182/blood.v97.12.3919

Cited by 122 publications

(81 citation statements)

References 47 publications

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“…This paracrine interaction would result in a positive feedback loop that may enhance both angiogenesis and tumor cell proliferation. 48,49 Co-expression of both VEGF and VEGF receptors in leukemia, lymphoma and multiple myeloma coupled with its direct effects on tumor cell survival migration, and proliferation, confirms the pivotal role for autocrine VEGF loops in the pathogenesis of these malignancies. 50 On the other hand, it should be mentioned that in addition to its role as an essential regulator of physiologic and pathologic angiogenesis, as demonstrated for TF, VEGF holds a number of recently proved additional roles.…”

Section: Angiogenesis In Hematologic Malignanciesmentioning

confidence: 99%

“…84 In that way, it has been recently shown that in acute promyelocytic leukemia (APL) cells, ATRA therapy inhibits VEGF production and suppresses angiogenesis. 49 It is well known that VEGF also stimulates TF production, which is significantly increased in this AML subtype as well. ATRA also reduces the procoagulant potential of malignant cells and modulates a number of hemostatic properties of normal endothelium and monocytes, including the increase in thrombomodulin (TM) expression and enhanced profibrinolytic functions.…”

Section: Tf-and Vegf-targeted Cancer Therapy In Hematological Malignamentioning

confidence: 99%

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Tissue factor as an effector of angiogenesis and tumor progression in hematological malignancies

et al. 2006

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Section: Angiogenesis In Hematologic Malignanciesmentioning

confidence: 99%

Section: Tf-and Vegf-targeted Cancer Therapy In Hematological Malignamentioning

confidence: 99%

Tissue factor as an effector of angiogenesis and tumor progression in hematological malignancies

et al. 2006

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“…24,38 Recently, an important role for angiogenesis in patients with leukemia has been shown, [39][40][41][42][43] raising the possibility of a role of anti-angiogenic drugs in the treatment of these types of cancer. By blocking VEGF secretion, aplidine, apart from its ability to induce growth factor deprivation, could affect angiogenesis in hematopoietic malignancies.…”

Section: Figure 10mentioning

confidence: 99%

Aplidine, a new anticancer agent of marine origin, inhibits vascular endothelial growth factor (VEGF) secretion and blocks VEGF-VEGFR-1 (flt-1) autocrine loop in human leukemia cells MOLT-4

et al. 2003

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The mechanism by which aplidine, a marine natural product in early clinical development as an anticancer agent, induces cell growth inhibition and apoptosis has been investigated in the human leukemia cell line MOLT-4. This cell line is characterized not only by the ability to secrete VEGF, but also for the presence on its surface of the VEGF receptor-1 (VEGFR-1). Previous studies from our laboratory concerned with evaluating early changes in gene expression induced by aplidine in MOLT-4 cells have shown that the drug decreases the expression of VEGFR-1 (Marchini et al. Proc Am Assoc Cancer Res 2000; 41: 833). Here, we report the ability of aplidine to block the VEGF/VEGFR-1 loop. We found that aplidine blocked VEGF secretion that was temporally followed by a decrease in both VEGF and VEGFR-1 production. Aplidine did not directly affect either VEGF transcription or stabilization of its mRNA. Transfection of MOLT-4 cells with an antisense VEGF cDNA construct, resulted in inhibition of colony formations. One clone, transfected with sense VEGF cDNA, secreting 8-10 times more VEGF than parental cells, was less sensitive to aplidineinduced cytotoxicity and apoptosis than control cells. Moreover, addition of VEGF in the medium decreased the activity of aplidine in MOLT-4 cells. These data demonstrate that aplidine inhibits the growth and induces apoptosis in MOLT-4 cells through the inhibition of VEGF secretion which blocks the VEGF/VEGFR-1 autocrine loop necessary for the growth of these cells.

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“…Thus, patients with acute lymphocytic leukemia, acute myeloid leukemia, non-Hodgkin's lymphoma, multiple myeloma, myelofibrosis and acute promyelocytic leukemia were shown to have increases in bone marrow microvessel density. [6][7][8][9][10][11][12][13] Recently, we and others [14][15][16][17][18] have defined a variety of abnormalities in the angiogenic status of patients with B-chronic lymphocytic leukemia (B-CLL). These abnormalities have included increased microvessel density in marrow 14 and lymph nodes 15 and increased levels of certain pro-angiogenic vascular growth factors including basic fibroblast growth factor (bFGF) and vascular endothelial cell growth factor (VEGF) in blood and urine of B-CLL patients.…”

Section: -3mentioning

confidence: 99%

B-CLL cells are capable of synthesis and secretion of both pro- and anti-angiogenic molecules

et al. 2002

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Initial work has shown that clonal B cells from B-chronic lymphocytic leukemia (B-CLL) are able to synthesize pro-angiogenic molecules. In this study, our goal was to study the spectrum of angiogenic factors and receptors expressed in the CLL B cell. We used ELISA assays to determine the levels of basic fibroblast growth factors (bFGF), vascular endothelial growth factor (VEGF), endostatin, interferon-␣ (IFN-␣) and thrombospondin-1 (TSP-1) secreted into culture medium by purified CLL B cells. These data demonstrated that CLL B cells spontaneously secrete a variety of pro-and anti-angiogenic factors, including bFGF (23.9 pg/ml ± 7.9; mean ± s.e.m.), VEGF (12.5 pg/ml ± 2.3) and TSP-1 (1.9 ng/ml ± 0.3). Out of these three factors, CLL B cells consistently secreted bFGF and TSP-1, while VEGF was expressed in approximately two-thirds of CLL patients. Of interest, hypoxic conditions dramatically upregulated VEGF expression at both the mRNA and protein levels. We also employed ribonuclease protection assays to assay CLL B cell expression of a variety of other angiogenesis-related molecules. These analyses revealed that CLL B cells consistently express mRNA for VEGF receptor 1 (VEGFR1), thrombin receptor, endoglin, and angiopoietin. Further analysis of VEGFR expression by RT-PCR revealed that CLL B cells expressed both VEGFR1 mRNA and VEGFR2 mRNA. In summary, these data collectively indicate that CLL B cells express both proand anti-angiogenic molecules and several vascular factor receptors. Because of the co-expression of angiogenic molecules and receptors for some of these molecules, these data suggest that the biology of the leukemic cells may also be directly impacted by angiogenic factors as a result of autocrine pathways of stimulation. Leukemia (2002) 16, 911-919.

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Angiogenesis in acute promyelocytic leukemia: induction by vascular endothelial growth factor and inhibition by all-trans retinoic acid

Cited by 122 publications

References 47 publications

Tissue factor as an effector of angiogenesis and tumor progression in hematological malignancies

Tissue factor as an effector of angiogenesis and tumor progression in hematological malignancies

Aplidine, a new anticancer agent of marine origin, inhibits vascular endothelial growth factor (VEGF) secretion and blocks VEGF-VEGFR-1 (flt-1) autocrine loop in human leukemia cells MOLT-4

B-CLL cells are capable of synthesis and secretion of both pro- and anti-angiogenic molecules

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