The C-terminal CD47/IAP-binding domain of thrombospondin-1 prevents camptothecin- and doxorubicin-induced apoptosis in human thyroid carcinoma cells

Rath, Géraldine; Schneider, Christophe; Dedieu, Stéphane; Rothhut, Bernard; Soula-Rothhut, Mahdhia; Ghoneim, Christelle; Sid, Brice; Morjani, Hamid; Btaouri, Hassan El; Martiny, Laurent

doi:10.1016/j.bbamcr.2006.08.001

Cited by 47 publications

(48 citation statements)

References 52 publications

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“…TSP-1 has been used for anticancer therapeutic trials, using both the whole molecule (3,106) and modules such as the TSP-1 repeats (146,147) or the peptides thereof (110), which are antiangiogenic. Other modules such as the CD47 binding domain counteracted chemotherapy by inhibiting apoptosis (104). As implicated in our study, proteolytic processing of TSP-1 could regulate the modules which are available for interaction and hence modulate the overall effect of TSP-1 on tumorigenesis.…”

Section: Discussionmentioning

confidence: 94%

Pharmacoproteomics of a Metalloproteinase Hydroxamate Inhibitor in Breast Cancer Cells: Dynamics of Membrane Type 1 Matrix Metalloproteinase-Mediated Membrane Protein Shedding

Butler¹,

Dean²,

Tam

et al. 2008

Molecular and Cellular Biology

144

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Broad-spectrum matrix metalloproteinase (MMP) inhibitors (MMPI) were unsuccessful in cancer clinical trials, partly due to side effects resulting from limited knowledge of the full repertoire of MMP substrates, termed the substrate degradome, and hence the in vivo functions of MMPs. To gain further insight into the degradome of MMP-14 (membrane type 1 MMP) an MMPI, prinomastat (drug code AG3340), was used to reduce proteolytic processing and ectodomain shedding in human MDA-MB-231 breast cancer cells transfected with MMP-14. We report a quantitative proteomic evaluation of the targets and effects of the inhibitor in this cell-based system. Proteins in cell-conditioned medium (the secretome) and membrane fractions with levels that were modulated by the MMPI were identified by isotope-coded affinity tag (ICAT) labeling and tandem mass spectrometry. Comparisons of the expression of MMP-14 with that of a vector control resulted in increased MMP-14/vector ICAT ratios for many proteins in conditioned medium, indicating MMP-14-mediated ectodomain shedding. Following MMPI treatment, the MMPI/vehicle ICAT ratio was reversed, suggesting that MMP-14-mediated shedding of these proteins was blocked by the inhibitor. The reduction in shedding or the release of substrates from pericellular sites in the presence of the MMPI was frequently accompanied by the accumulation of the protein in the plasma membrane, as indicated by high MMPI/vehicle ICAT ratios. Considered together, this is a strong predictor of biologically relevant substrates cleaved in the cellular context that led to the identification of many undescribed MMP-14 substrates, 20 of which we validated biochemically, including DJ-1, galectin-1, Hsp90␣, pentraxin 3, progranulin, Cyr61, peptidyl-prolyl cis-trans isomerase A, and dickkopf-1. Other proteins with altered levels, such as Kunitz-type protease inhibitor 1 and beta-2-microglobulin, were not substrates in biochemical assays, suggesting an indirect affect of the MMPI, which might be important in drug development as biomarkers or, in preclinical phases, to predict systemic drug actions and adverse side effects. Hence, this approach describes the dynamic pattern of cell membrane ectodomain shedding and its perturbation upon metalloproteinase drug treatment.The membrane type 1 matrix metalloproteinase (MMP-14) is a member of the MMP family of zinc-dependent endoproteinases that are important in cancer (31, 92), consisting of 23 members in humans, 6 of which (including MMP-14) are membrane anchored (50, 122). The MMPs are one of four families of the metzincin clan, which includes ADAM (a disintegrinlike and metalloprotease domain) and ADAM with thrombospondin type 1 motifs (ADAM-TS) extracellular proteases (40). MMP-14 is constitutively activated in the Golgi apparatus by furin and, at the cell surface, undergoes autodegradation which removes and inactivates the catalytic domain, leaving a remnant ectodomain composed of the linker and hemopexin C domains (50). The hemopexin C domain encompasses binding sites known as...

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Section: Discussionmentioning

confidence: 94%

Pharmacoproteomics of a Metalloproteinase Hydroxamate Inhibitor in Breast Cancer Cells: Dynamics of Membrane Type 1 Matrix Metalloproteinase-Mediated Membrane Protein Shedding

Butler¹,

Dean²,

Tam

et al. 2008

Molecular and Cellular Biology

144

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“…S4), suggesting some potential common mechanisms for both types of resistance to BMS-536924. These genes are all somehow involved in drug resistance (43)(44)(45); further study of their roles in resistance to BMS-536924 is warranted.…”

Section: Discussionmentioning

confidence: 99%

The Mechanisms of Differential Sensitivity to an Insulin-like Growth Factor-1 Receptor Inhibitor (BMS-536924) and Rationale for Combining with EGFR/HER2 Inhibitors

et al. 2008

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“…Moreover, this apoptosis is accompanied by a downregulation of TSP-1 expression at mRNA and protein levels [39]. The addition of TSP-1 protects the cells against doxorubicin-induced apoptosis [39]. The antiapoptotic role of TSP-1 involves its C-terminal part that interacts with the membrane receptor CD47.…”

Section: Modulation Of Chemotherapy-induced Apoptosis By Extracellmentioning

confidence: 99%

Extracellular Matrix Proteins Modulate Antimigratory and Apoptotic Effects of Doxorubicin

Said

Guilbert

Morjani

et al. 2012

Chemotherapy Research and Practice

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Anticancer drug resistance is a multifactorial process that includes acquired and de novo drug resistances. Acquired resistance develops during treatment, while de novo resistance is the primary way for tumor cells to escape chemotherapy. Tumor microenvironment has been recently shown to be one of the important factors contributing to de novo resistance and called environment-mediated drug resistance (EMDR). Two forms of EMDR have been described: soluble factor-mediated drug resistance (SFM-DR) and cell adhesion-mediated drug resistance (CAM-DR). Anthracyclines, among the most potent chemotherapeutic agents, are widely used in clinics against hematopoietic and solid tumors. Their main mechanism of action relies on the inhibition of topoisomerase I and/or II and the induction of apoptosis. Beyond this well-known antitumor activity, it has been recently demonstrated that anthracyclines may display potent anti-invasive effects when used at subtoxic concentrations. In this paper, we will describe two particular modes of EMDR by which microenvironment may influence tumor-cell response to one of these anthracyclines, doxorubicin. The first one considers the influence of type I collagen on the antimigratory effect of doxorubicin (CAM-DR). The second considers the protection of tumor cells by thrombospondin-I against doxorubicin-induced apoptosis (SFM-DR).

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The C-terminal CD47/IAP-binding domain of thrombospondin-1 prevents camptothecin- and doxorubicin-induced apoptosis in human thyroid carcinoma cells

Cited by 47 publications

References 52 publications

Pharmacoproteomics of a Metalloproteinase Hydroxamate Inhibitor in Breast Cancer Cells: Dynamics of Membrane Type 1 Matrix Metalloproteinase-Mediated Membrane Protein Shedding

Pharmacoproteomics of a Metalloproteinase Hydroxamate Inhibitor in Breast Cancer Cells: Dynamics of Membrane Type 1 Matrix Metalloproteinase-Mediated Membrane Protein Shedding

The Mechanisms of Differential Sensitivity to an Insulin-like Growth Factor-1 Receptor Inhibitor (BMS-536924) and Rationale for Combining with EGFR/HER2 Inhibitors

Extracellular Matrix Proteins Modulate Antimigratory and Apoptotic Effects of Doxorubicin

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