Histopathological findings in a highly invasive mouse mammary carcinoma transfected with human tissue inhibitor of metalloproteinases-1.

Alonso, Daniel F.; Skilton, G; Lorenzo, Mariana S. De; Scursoni, Alejandra M.; Yoshiji, Hitoshi; Gómez, Daniel E.

doi:10.3892/or.5.5.1083

Cited by 7 publications

(4 citation statements)

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“…Inhibition of cancer cell invasion after overexpression of TIMPs using different gene delivery vectors has been shown in vitro in gastric cancer cells and mammary carcinoma cells (156,157). Overexpression in vitro of TIMP-2, which was delivered by a recombinant adenovirus (AdTIMP-2), inhibited the invasion of both tumor and endothelial cells in three murine models without affecting cell proliferation (158).…”

Section: Matrix Metalloproteinasementioning

confidence: 99%

Burger's Medicinal Chemistry and Drug Discovery

Abraham¹

2003

142

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Section: Matrix Metalloproteinasementioning

confidence: 99%

Burger's Medicinal Chemistry and Drug Discovery

Abraham¹

2003

142

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“…TIMP-1 was originally identified as a naturally occurring intrinsic barrier to tumor invasion [15, 16]. However, studies on cancer proliferation and growth have shown both pro- and anti-tumorigenic effects for TIMP-1 depending on the tumor and concentration of protein expressed [17–22]. …”

Section: Introductionmentioning

confidence: 99%

Recombinant TIMP-1-GPI inhibits growth of fibrosarcoma and enhances tumor sensitivity to doxorubicin

Bao

Nieß²,

Djafarzadeh

et al. 2013

Targ Oncol

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Fibrosarcomas show a high incidence of recurrence and general resistance to apoptosis. Limiting tumor regrowth and increasing their sensitivity to chemotherapy and apoptosis represent key issues in developing more effective treatments of these tumors. Tissue inhibitor of metalloproteinase 1 (TIMP-1) broadly blocks matrix metalloproteinase (MMP) activity and can moderate tumor growth and metastasis. We previously described generation of a recombinant fusion protein linking TIMP-1 to glycosylphophatidylinositol (GPI) anchor (TIMP-1-GPI) that efficiently directs the inhibitor to cell surfaces. In the present report, we examined the effect of TIMP-1-GPI treatment on fibrosarcoma biology. Exogenously applied TIMP-1-GPI efficiently incorporated into surface membranes of human HT1080 fibrosarcoma cells. It inhibited their proliferation, migration, suppressed cancer cell clone formation, and enhanced apoptosis. Doxorubicin, the standard chemotherapeutic drug for fibrosarcoma, was tested alone or in combination with TIMP-1-GPI. In parallel, the influence of treatment on HT1080 side population cells (exhibiting tumor stem cell-like characteristics) was investigated using Hoechst 33342 staining. The sequential combination of TIMP-1-GPI and doxorubicin showed more than additive effects on apoptosis, while TIMP-1-GPI treatment alone effectively decreased “stem-cell like” side population cells of HT1080. TIMP-1-GPI treatment was validated using HT1080 fibrosarcoma murine xenografts. Growing tumors treated with repeated local injections of TIMP-1-GPI showed dramatically inhibited fibrosarcoma growth and reduced angiogenesis. Intraoperative peritumoral application of GPI-anchored TIMP-1 as an adjuvant to surgery may help maintain tumor control by targeting microscopic residual fibrosarcoma cells and increasing their sensitivity to chemotherapyElectronic supplementary materialThe online version of this article (doi:10.1007/s11523-013-0294-5) contains supplementary material, which is available to authorized users.

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“…Overexpression of TIMP-1 in gastric cancer cells reduced metastasis of clones expressing high levels of TIMP-1 [130]. TIMP-1 also reduced the growth rate and inhibited invasion of astrocytoma cells [131], prevented metastasis of gastric cancer cells [132] and inhibited invasion and growth of mammary carcinoma cells [133]. The ability of TIMP-1 to alter tumor development at different stages has been highlighted by the use of transgenic mice.…”

Section: Timps In Tumor Growth and Invasionmentioning

confidence: 99%

Matrix metalloproteinases in tumor invasion

Johansson

Ahonen

Kähäri

2000

Cellular and Molecular Life Sciences (CMLS)

292

198

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Controlled degradation of extracellular matrix (ECM) is essential for the growth, invasion, and metastasis of malignant tumors, and for tumor-induced angiogenesis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases collectively capable of degrading essentially all ECM components and they apparently play an important role in all these aspects of tumor development. Furthermore, recent evidence suggests that MMPs also play a role in tumor cell survival. In this review, we discuss the current concept concerning the role of MMPs and their inhibitors in tumor invasion, as a basis for prognosis and targeted therapeutic intervention in cancer.

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Histopathological findings in a highly invasive mouse mammary carcinoma transfected with human tissue inhibitor of metalloproteinases-1.

Cited by 7 publications

References 0 publications

Burger's Medicinal Chemistry and Drug Discovery

Burger's Medicinal Chemistry and Drug Discovery

Recombinant TIMP-1-GPI inhibits growth of fibrosarcoma and enhances tumor sensitivity to doxorubicin

Matrix metalloproteinases in tumor invasion

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