Targeting an MMP-9-activated prodrug to multiple myeloma-diseased bone marrow: a proof of principle in the 5T33MM mouse model

Valckenborgh, Els Van; Mincher, David J.; Salvo, Alberto Di; Riet, Ivan Van; Young, Lesley; Camp, Benjamin Van; Vanderkerken, Karin

doi:10.1038/sj.leu.2403866

Cited by 32 publications

(22 citation statements)

References 22 publications

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“…MM cells were shown to constitutively produce MMP-9. 79,80 Similar results were observed with a VLA-4 (␣4␤1) inhibitory antibody 28 or with a selective antibody Natalizumab (Biogen Idec). 81 Similarly, P-selectin glycoprotein ligand-1 knockdown or inhibition by a small pan-selectin inhibitor (GMI-1070; Glycomimetics) showed significant inhibition of rolling and homing in vitro and in vivo.…”

Section: Circulation In the Peripheral Bloodsupporting

confidence: 67%

Myeloma as a model for the process of metastasis: implications for therapy

Ghobrial

2012

Blood

173

172

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Multiple myeloma (MM) is a plasma cell dyscrasia characterized by the presence of multiple myelomatous "omas" throughout the skeleton, indicating that there is continuous trafficking of tumor cells to multiple areas in the bone marrow niches. MM may therefore represent one of the best models to study cell trafficking or cell metastasis. The process of cell metastasis is described as a multistep process, the invasion-metastasis cascade. This involves cell invasion, intravasation into nearby blood vessels, passage into the circulation, followed by homing into predetermined distant tissues, the formation of new foci of micrometastases, and finally the growth of micrometastasis into macroscopic tumors. This review discusses the significant advances that have been discovered in the complex process of invasion-metastasis in epithelial carcinomas and cell trafficking in hematopoietic stem cells and how this process relates to progression in MM. This progression is mediated by clonal intrinsic factors that mediate tumor invasiveness as well as factors present in the tumor microenvironment that are permissive to oncogenic proliferation. Therapeutic agents that target the different steps of cell dissemination and progression are discussed. Despite the significant advances in the treatment of MM, better therapeutic agents that target this metastatic cascade are urgently needed. IntroductionMultiple myeloma (MM) is a plasma cell dyscrasia characterized by the presence of multiple lytic lesions at the time of diagnosis. 1,2 The presence of multiple myelomatous "omas" throughout the axial skeleton detected at the time of diagnosis in most patients indicates that there is continuous spread or dissemination of tumor cells from the original site of tumor development to multiple sites in the BM niches, leading to the final development of symptomatic disease. Therefore, MM may represent a good model disease to study cell trafficking or cell metastasis. Although the term "metastasis" is not commonly used to describe dissemination of hematologic malignancies, this review attempts to examine how MM can use a process of cell dissemination that is similar to cell trafficking of hematopoietic stem cell (HSCs) and cell metastasis in solid epithelial carcinomas. These studies can guide our understanding of the biologic changes that occur during progression in MM. Cell metastasis and cell traffickingThe process of cell metastasis is usually described as a multistep process, often termed as the invasion-metastasis cascade. [3][4][5][6] This involves several steps of changes that include: (1) cell invasion, (2) intravasation (egress) into nearby blood vessels, (3) passage of the tumor cells into the circulation, followed by (4) homing or extravasation of tumor cells from these vessels into the specific predetermined distant tissues, (5) the formation of new foci of tumor micrometastases, and (6) finally the growth of micrometastatic lesions into macroscopic tumors, a step called "colonization."A similar process occurs with cell trafficking ...

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Section: Circulation In the Peripheral Bloodsupporting

confidence: 67%

Myeloma as a model for the process of metastasis: implications for therapy

Ghobrial

2012

Blood

173

172

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“…Elevated levels of distinct MMP can be detected in serum of patients with advanced cancer, and their role as prognostic indicators in cancer has been widely examined [39]. Our results are consistent with Van Valckenborgh et al [40] who found that an anticancer compound (resveratrol) suppressed the activity of MMP-2 and MMP-9. It has been reported that a significant increase in MMP activity occurs in the bone marrow environment of patients with myeloma [41].…”

Section: Discussionsupporting

confidence: 95%

Chitosan and marine phospholipids reduce matrix metalloproteinase activity in myeloma SP2 tumor‐bearing mice

Hossain

Fukunaga

Tanouchi³

et al. 2009

Euro J Lipid Sci & Tech

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An animal experiment was conducted to assess the antitumor effects of chitosan-coated liposomes on myeloma SP2. The animal experimental groups designed for myeloma SP2 tumor-bearing BALB/c mice were provided with five different drinks: (I) control (double-distilled water); (II) squid phospholipid liposomes alone 1.0 mg/mL; (III) chitosan alone 5.0 mg/mL; (IV) squid phospholipid liposomes 1.0 mg/ mL with chitosan 5.0 mg/mL in the form of a simple mixture; and (V) squid phospholipid liposomes 1.0 mg/mL coated with chitosan 5.0 mg/mL. At 20 days after implantation of the myeloma SP2 cells into mice, oral administration of the experimental drinks was provided for 35 days. There was significant suppression of tumor growth when chitosan and squid phospholipids were administered simultaneously in a simple mixture or as chitosan-coated liposomes. Matrix metalloproteinase (MMP)-2 and MMP-9 activity was significantly less in the serum of mice that consumed chitosan-coated liposomes than in control mice. We found that decreased tumor burden was related to MMP secretion. Therefore, chitosan-coated marine phospholipid liposomes might be useful as potential agents for the treatment of myeloma SP2.

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“…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]. Since levels of MMP-9, a mediator of tumor invasion, are increased in multiple types of hematological malignancies, it will be important to develop drugs that target MMPs.…”

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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Targeting an MMP-9-activated prodrug to multiple myeloma-diseased bone marrow: a proof of principle in the 5T33MM mouse model

Cited by 32 publications

References 22 publications

Myeloma as a model for the process of metastasis: implications for therapy

Myeloma as a model for the process of metastasis: implications for therapy

Chitosan and marine phospholipids reduce matrix metalloproteinase activity in myeloma SP2 tumor‐bearing mice

Targeting Cyclooxygenase-2 in Hematological Malignancies: Rationale and Promise

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