New Functions of Stromal Proteases and Their Inhibitors in Tumor Progression

Noël, Agnès; Albert, Valérie; Bajou, Khalid; Bisson, Christèle; Devy, Laetitia; Frankenne, Françis; Maquoi, Erik; Masson, Véronique; Sounni, Nor Eddine; Foidart, Jean Michel

doi:10.1016/s1055-3207(18)30073-5

Cited by 21 publications

(22 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several proteinases are able to control the bioavailability and activity of growth factors (8,9). These effects rely on the release of active molecules from the ECM, the cleavage of growth factors binding proteins, or the shedding of receptor ligands from the cell surface (9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

“…These effects rely on the release of active molecules from the ECM, the cleavage of growth factors binding proteins, or the shedding of receptor ligands from the cell surface (9)(10)(11)(12). Among proteinases that modulate growth factor/growth factor receptor activities or bioavailability are the zinc-binding endopeptidase family including matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM; refs.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

EGFR Activation and Signaling in Cancer Cells Are Enhanced by the Membrane-Bound Metalloprotease MT4-MMP

et al. 2014

Self Cite

View full text Add to dashboard Cite

MT4-MMP (MMP-17) is a glycosylphosphatidyl inositol-anchored matrix metalloprotease expressed on the surface of cancer cells that promotes tumor growth and metastasis. In this report, we identify MT4-MMP as an important driver of cancer cell proliferation through CDK4 activation and retinoblastoma protein inactivation. We also determine a functional link between MT4-MMP and the growth factor receptor EGFR. Mechanistic experiments revealed direct association of MT4-MMP and its positive effects on EGFR phosphorylation in response to TGFa and EGF in cancer cells. Notably, the effects of MT4-MMP on proliferation and EGFR activation did not rely on metalloprotease activity. Clinically, MT4-MMP and EGFR expressions were correlated in human triple-negative breast cancer specimens. Altogether, our results identify MT4-MMP as a positive modifier of EGFR outside-in signaling that acts to cooperatively drive cancer cell proliferation. Cancer Res; 74(23); 6758-70. Ó2014 AACR.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

EGFR Activation and Signaling in Cancer Cells Are Enhanced by the Membrane-Bound Metalloprotease MT4-MMP

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…An important role for myofibroblasts was suggested by the fact that large numbers of myofibroblasts were found near the invasive front of colon cancer or other invasive carcinomas (Nakayama et al, 1998). Recently, it became evident that MMPs are mostly produced by stromal cells and not by the cancer cells (Noël et al, 2001). The cancer cells can recruit host cells, such as myofibroblasts, to become proteinase factories.…”

Section: Discussionmentioning

confidence: 99%

Invasion and MMP expression profile in desmoid tumours

et al. 2004

View full text Add to dashboard Cite

Desmoid tumours are locally invasive soft tissue tumours in which b-catenin mediated TCF-dependent transcription is activated. The role of soluble factors secreted by the myofibroblastic desmoid tumour, which could stimulate tumour invasiveness, was investigated. Using collagen gel invasion assays, the presence of factors stimulating invasion in desmoid conditioned media (CM) could be established. Since matrix metalloproteinases (MMPs) have been implicated in the process of tumoral invasion, the expression levels of the MMP family members were evaluated. Quantitative reverse transcription -PCR was used to determine the expression levels of MMP1, MMP2, MMP3, MMP7, MMP11, MMP12, MMP13, MMP14 and the inhibitors TIMP1, TIMP2 and TIMP3. Besides overexpression of MMP7, a known TCF-dependent target gene, a striking upregulation of the expression levels of MMP1, MMP3, MMP11, MMP12 and MMP13 in desmoid tumours, compared to unaffected fibroblasts from the same patients, was found. Treating the CM of desmoids with a synthetic and a physiologic MMP inhibitor reduced the invasion-stimulating capacity of the desmoid CM by approximately 50%. These results suggest the involvement of soluble factors, released by the desmoid cells, in stimulating invasion and implicate the MMPs as facilitators of invasion.

show abstract

“…Approximately 50% of cancer patients die because the initial tumor becomes metastatic [1]. Several studies have demonstrated a positive correlation between tumor progression and expression of extracellular proteinases such as matrix metalloproteinases (MMPs) [2][3][4][5]. In addition, high MMP levels were associated with poor prognosis in cancer patients.…”

Section: Introductionmentioning

confidence: 99%

“…MMPs are proteolytic enzymes and their basic mechanism of action-degradation of extracellular matrix components (ECM)-regulates various cell behaviours with relevance for cancer biology [6]. These include cancer cell growth migration, invasion, and the regulation of tumor angiogenesis [5][6][7][8][9] . The MMP family is now known to include at least 20 enzymes and is categorized into several classes based on substrate specificity and domain structure [10].…”

Section: Introductionmentioning

confidence: 99%

New radioiodinated carboxylic and hydroxamic matrix metalloproteinase inhibitor tracers as potential tumor imaging agents

Oltenfreiter

Staelens

Lejeune

et al. 2004

Nuclear Medicine and Biology

Self Cite

View full text Add to dashboard Cite

Several studies have demonstrated a positive correlation between tumor progression and expression of extracellular proteinases such as matrix metalloproteinases (MMPs). MMP-2 and MMP-9 have become attractive targets for cancer research because of their increased expression in human malignant tumor tissues of various organs, providing a target for medical imaging techniques. Radioiodinated carboxylic and hydroxamic MMP inhibitors 2-(4'-[ (11) were synthesized by electrophilic aromatic substitution of the tributylstannyl derivatives and resulted in radiochemical yields of 60% ± 5% (n = 3) and 70% ± 5% (n = 6), respectively. In vitro zymography and enzyme assays showed high inhibition capacities of the inhibitors on gelatinases. In vivo biodistribution showed no long-term accumulation in organs and the possibility to accumulate in the tumor. These results warrant further studies of radioiodinated carboxylic and hydroxamic MMP inhibitor tracers as potential SPECT tumor imaging agents.

show abstract

New Functions of Stromal Proteases and Their Inhibitors in Tumor Progression

Cited by 21 publications

References 81 publications

EGFR Activation and Signaling in Cancer Cells Are Enhanced by the Membrane-Bound Metalloprotease MT4-MMP

EGFR Activation and Signaling in Cancer Cells Are Enhanced by the Membrane-Bound Metalloprotease MT4-MMP

Invasion and MMP expression profile in desmoid tumours

New radioiodinated carboxylic and hydroxamic matrix metalloproteinase inhibitor tracers as potential tumor imaging agents

Contact Info

Product

Resources

About