Leukomogenic factors downregulate heparanase expression in acute myeloid leukemia cells

Eshel, Rinat; Ben-Zaken, Olga; Vainas, Oded; Nadir, Yona; Minucci, Saverio; Polliack, Aaron; Naparstek, E; Vlodavsky, Israël; Katz, Ben Z.

doi:10.1016/j.bbrc.2005.08.004

Cited by 7 publications

(7 citation statements)

References 32 publications

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“…Previous studies 11,14 indicated that heparanase plays a role in the normal function of hematopoietic cells. Presumably, heparanase may be involved in differentiation of hematopoietic cells by releasing HS-bound bioactive mediators (that is, cytokines, chemokines), which may, among other effects, regulate gene expression.…”

Section: Discussionmentioning

confidence: 99%

“…5,28 Reduction or loss of heparanase activity may be associated with de-differentiation of leukemic cells. 14 Whether gene transcription and maintained cellular differentiation is due to direct interaction of heparanase with the DNA, or is a consequence of heparanase-mediated degradation of nuclear HS, is yet to be demonstrated. 8,9 MM is a B-lymphoid malignancy characterized by tumor cell infiltration of the bone marrow, osteolytic lesions and angiogenesis in the vicinity of the tumor cells.…”

Section: Discussionmentioning

confidence: 99%

“…11 As the development of malignancy is associated with a loss of normal functions characteristic of mature cells, reduction or loss of heparanase activity may be associated with de-differentiation of hematopoietic cells. 14 However, the possible involvement of heparanase in hematological malignancies was not assessed systematically.…”

Section: Introductionmentioning

confidence: 99%

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Association of heparanase gene (HPSE) single nucleotide polymorphisms with hematological malignancies

et al. 2007

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Association of heparanase gene (HPSE) single nucleotide polymorphisms with hematological malignancies

et al. 2007

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“…RT-PCR was carried out on 2Â reaction mixtures in the presence of 0.4 mM each dNTP, 0.2 mM gene specific primers and cDNA synthesis was followed immediately by PCR amplification, as follow: cDNA synthesis (1 cycle: 558C for 40 min), Denaturation (1 cycle: 948C for 2 min), PCR amplification (35 cycles: 948C for 20 sec, 558C for 20 sec, 728C for 40 sec), and final extension (1 cycle: 728C for 7 min). LPA 1 , LPA 2 , and LPA 3 receptor primers were as follows LPA 1 forward: 5 0 -ATCTTTGGCTATGTTCGCCA-3 0 and reverse: 5 0 -TTGCTGTGAACTCCAGCCA-3 0 ; LPA 2 forward: 5 0 -TGGCCTACCCTTCCTCATGTTCCA-3 0 and reverse: 5 0 -GACCAGTGAGTTGGCCTCAGC-3 0 , LPA 3 forward: 5 0 -GAGGATGAGAGTCCACAG-3 0 and reverse: 5 0 -GCACAGCAGATCATCTTC-3 0 (Chun et al, 1999;Eshel et al, 2005). For real-time PCR, we used the SuperScript first-strand synthesis system (Invitrogen) and prepared cDNA from 1 mg of RNA.…”

Section: Methodsmentioning

confidence: 99%

LPA₁‐induced migration requires nonmuscle myosin II light chain phosphorylation in breast cancer cells

Kim

Adelstein

2011

Journal Cellular Physiology

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The enhanced migration found in tumor cells is often caused by external stimuli and the sequential participation of cytoskeleton-related signaling molecules. However, until now, the molecular connection between the lysophosphatidic acid (LPA) receptor and nonmuscle myosin II (NM II) has not been analyzed in detail for LPA-induced migration. Here, we demonstrate that LPA induces migration by activating the LPA 1 receptor which promotes phosphorylation of the 20kDa NM II light chain through activation of Rho kinase (ROCK). We show that LPA-induced migration is insensitive to pertussis toxin (PTX) but does require the LPA 1 receptor as determined by siRNA and receptor antagonists. LPA activates ROCK and also increases GTP-bound RhoA activity, concomitant with the enhanced membrane recruitment of RhoA. LPA-induced migration and invasion are attenuated by specific inhibitors including C3 cell-permeable transferase and Y-27632. We demonstrate that NM II plays an important role in LPA-induced migration and invasion by inhibiting its cellular function with blebbistatin and shRNA lentivirus directed against NM II-A or II-B. Inhibition or loss of either NM II-A or NM II-B in 4T1 cells results in a decrease in migration and invasion. Restoration of the expression of NM II-A or NM II-B also rescued LPA-induced migration. Taken together, these results suggest defined pathways for signaling through the LPA 1 receptor to promote LPA-mediated NM II activation and subsequent cell migration in 4T1 breast cancer cells.

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“…Downregulation of heparanase expression has been reported in acute promyelocytic leukemia, the leukemia that responds well to differentiation therapies such as ATRA, with normalization of marrow vasculature (French–American–British, FAB: M3). 11, 26 …”

Section: Neoangiogenesis and Acute Leukemiamentioning

confidence: 99%

Contribution of bone microenvironment to leukemogenesis and leukemia progression

et al. 2009

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Tumor microenvironment has a major role in cancer progression and resistance to treatment. The bone marrow (BM) is a dynamic network of growth factors, cytokines and stromal cells, providing a permissive environment for leukemogenesis and progression. Both BM stroma and leukemic blasts promote angiogenesis, which is increased in acute lymphoblastic leukemia and acute myeloid leukemia. Growth factors like vascular endothelial growth factor (VEGF), basic fibroblast growth factor and angiopoietins are the main proangiogenic mediators in acute leukemia. Autocrine proleukemic loops have been described for VEGF and angiopoietin in hematopoietic cells. Interactions of stromal cells and extracellular matrix with leukemic blasts can also generate antiapoptotic signals that contribute to neoplastic progression and persistence of treatment-resistant minimal residual disease. High expression of CXC chemokine ligand 4 (CXCR4) by leukemic blasts and activation of the CXCR4–CXCL12 axis is involved in leukemia progression and disruption of normal hematopoiesis. Leukemia-associated bone microenvironment markers could be used as prognostic or predictive indicators of disease progression and/or treatment outcome. Studies related to bone microenvironment would likely provide a better understanding of the treatment resistance associated with leukemia therapy and design of new treatments.

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Leukomogenic factors downregulate heparanase expression in acute myeloid leukemia cells

Cited by 7 publications

References 32 publications

Association of heparanase gene (HPSE) single nucleotide polymorphisms with hematological malignancies

Association of heparanase gene (HPSE) single nucleotide polymorphisms with hematological malignancies

LPA₁‐induced migration requires nonmuscle myosin II light chain phosphorylation in breast cancer cells

Contribution of bone microenvironment to leukemogenesis and leukemia progression

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Leukomogenic factors downregulate heparanase expression in acute myeloid leukemia cells

Cited by 7 publications

References 32 publications

Association of heparanase gene (HPSE) single nucleotide polymorphisms with hematological malignancies

Association of heparanase gene (HPSE) single nucleotide polymorphisms with hematological malignancies

LPA1‐induced migration requires nonmuscle myosin II light chain phosphorylation in breast cancer cells

Contribution of bone microenvironment to leukemogenesis and leukemia progression

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LPA₁‐induced migration requires nonmuscle myosin II light chain phosphorylation in breast cancer cells