Production of matrix metalloproteinase-9 in early stage B-CLL: suppression by interferons

Bauvois, Brigitte; Dumont, J; Mathiot, Claire; Jp, Kolb

doi:10.1038/sj.leu.2402472

Cited by 89 publications

(90 citation statements)

References 52 publications

(62 reference statements)

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“…We reported previously that B-CLL leukemic cells express and release the pro-form of MMP-9, 5 Molica et al 6 made similar constatations and found that the serum level of MMP-9 in B-CLL patients is predictive of their outcome. High levels of intracellular MMP-9 were related to disease severity and poor patient survival, and MMP-9 associated with areas of tissue invasion and remodelling.…”

Section: Introductionmentioning

confidence: 65%

Hyperforin inhibits MMP-9 secretion by B-CLL cells and microtubule formation by endothelial cells

et al. 2006

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We previously reported that hyperforin (HF), a natural phloroglucinol purified from Saint John's wort, can induce the apoptosis of leukemic cells from patients with B-cell lymphocytic leukemia (B-CLL) ex vivo. We show here that treatment of cultured B-CLL patients' cells with HF results in a marked inhibition of their capacity to secrete matrix metalloproteinase-9, an essential component in neo-angiogenesis through degradation of the extracellular matrix process. The phloroglucinol acts by decreasing the production of the latent 92 kDa pro-enzyme. The inhibitory effect of HF is associated with a decrease in VEGF release by the leukemic cells. Moreover, HF is found to prevent the formation of microtubules by human bone marrow endothelial cells cultured on Matrigel, evidencing its capacity to inhibit vessel formation. Our results show the antiangiogenesis activity of HF and strengthen its potential interest in the therapy of B-CLL.

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Section: Introductionmentioning

confidence: 65%

Hyperforin inhibits MMP-9 secretion by B-CLL cells and microtubule formation by endothelial cells

et al. 2006

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“…32 TNFa itself is produced by B-CLL cells and contributes to cell survival in an autocrine manner. 33 Moreover, it has been reported by Bauvois et al 18 that TNFa upregulates MMP-9 secretion of B-CLL cells, suggesting a positive feed back mechanism. We investigated supernatants from CLL/stroma cocultures either untreated or treated with a blocking mAb against MMP-9 or SB203580 by ELISA.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, it has been reported that B-CLL cells synthesize matrix metalloproteinase-9 (MMP-9), 18 which plays a critical role in tumorangiogenesis and tumor homing. Elevated serum levels of MMP-9 might predict an early disease progression in B-CLL.…”

Section: Introductionmentioning

confidence: 99%

“…Cells were incubated in medium with or without the p38 kinase inhibitor SB203580 for 72 h and supernatants were analyzed by ELISA. Owing to the recent report that B-CLL cells synthesize angiogenetic factors like bFGF, VEGF and MMP-9, 18 we analyzed the contribution of p38 MAPK activity on the secretion of these soluble factors. The basal expression of VEGF and bFGF did not change due to the inhibition of p38 MAPK during in vitro culture of B-CLL cells (Figure 5b and c).…”

Section: P38 Regulates Secretion Of Mmp-9 In B-cll Cells But Not Of mentioning

confidence: 99%

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Constitutive activation of the MAPkinase p38 is critical for MMP-9 production and survival of B-CLL cells on bone marrow stromal cells

et al. 2004

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In the present work we investigated the role and biological significance of mitogen activated protein kinases (MAPK) in Bcell chronic lymphocytic leukaemia (B-CLL). The MAPK p38 was constitutively activated in B-CLL, but not in normal peripheral B cells. In addition, we demonstrated that the upstream kinases of p38, MKK3/6 were also constitutively activated in B-CLL cells. Furthermore, we determined by EMSA that the p38 MAP kinase pathway was not linked to the constitutive high expression of NF-jB, a critical survival factor of B-CLL cells. Recently, it has been shown that serum levels of angiogenic factors like VEGF, bFGF and MMP-9 are elevated in the serum of CLL patients and correlate with an unfavorable prognosis. We showed that the constitutive expression of MMP-9 was dependent on p38-activity and inhibition of p38 strongly downregulated MMP-9 expression. Coculture of B-CLL cells and stromal cells can protect spontaneous apoptosis of leukemic B cells. To determine the role of permanently activated p38 and MMP-9 expression, we cocultured B-CLL cells with bone marrow stromal cells. Survival of B-CLL cells on stroma was severely impaired when p38 was inhibited. Furthermore, blockade of MMP-9 activity also antagonized the antiapoptotic effect of stromal cells.

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“…Investigators have shown that MMP-9 can be expressed by adult T cell leukemia cells and that high levels correlated with increased metastases [80]. B-CLL cells expressed significant amounts of MMP-9, which was associated with increased invasion and lower patient survival rates [81,82]. One group has even developed a pro-drug that is activated by MMP-9 for MM therapy, as MM cells are known to overexpress MMP-9 [83].…”

Section: Cox-2/pge 2 Promotes Angiogenesis and Metastasismentioning

confidence: 99%

Targeting Cyclooxygenase-2 in Hematological Malignancies: Rationale and Promise

Bernard¹,

Bancos²,

Sime³

et al. 2008

CPD

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There is much interest in the potential use of Cox-2 selective inhibitors in combination with other cancer therapeutics. Malignancies of hematopoietic and non-hematopoietic origin often have increased expression of cyclooxygenase-2 (Cox-2), a key modulator of inflammation. For example, hematological malignancies such as chronic lymphocytic leukemia, chronic myeloid leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma and multiple myeloma often highly express Cox-2, which correlates with poor patient prognosis. Expression of Cox-2 enhances survival and proliferation of malignant cells, while negatively influencing anti-tumor immunity. Hematological malignancies expressing elevated levels of Cox-2 potentially avoid immune responses by producing factors that enhance angiogenesis and metastases. Cellular immune responses regulated by natural killer cells, cytotoxic T lymphocytes, and T regulatory cells are also influenced by Cox-2 expression. Therefore, Cox-2 selective inhibitors have promising therapeutic potential in patients suffering from certain hematological malignancies.

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Production of matrix metalloproteinase-9 in early stage B-CLL: suppression by interferons

Cited by 89 publications

References 52 publications

Hyperforin inhibits MMP-9 secretion by B-CLL cells and microtubule formation by endothelial cells

Hyperforin inhibits MMP-9 secretion by B-CLL cells and microtubule formation by endothelial cells

Constitutive activation of the MAPkinase p38 is critical for MMP-9 production and survival of B-CLL cells on bone marrow stromal cells

Targeting Cyclooxygenase-2 in Hematological Malignancies: Rationale and Promise

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