Journal ArticleDOI
Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment
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TLDR
The failure of MMPIs to alter disease progression in metastatic cancer might have been anticipated since MMPs appear to be important in early aspects of cancer progression (local invasion and micrometastasis) and may no longer be required once metastases have been established.Abstract:
Experimental studies performed prior to 1990 led to the widely held belief that matrix metalloproteinases (MMPs) produced by cancer cells are of critical importance in tumor invasion and metastasis. Based on this evidence, the pharmaceutical industry produced several well tolerated, orally active MMP inhibitors (MMPIs) which demonstrated efficacy in mouse cancer models. Phase III clinical trials initiated in 1997-98 using marimastat, prinomastat (AG3340), and BAY 12-9566 alone or in combination with standard chemotherapy in patients with advanced cancers (lung, prostate, pancreas, brain, GI tract) have recently been reported; no clinical efficacy was demonstrated. Bayer and Agouron have discontinued their ongoing Phase III drug trials of MMPIs in advanced cancer. In retrospect, the failure of MMPIs to alter disease progression in metastatic cancer might have been anticipated since MMPs appear to be important in early aspects of cancer progression (local invasion and micrometastasis) and may no longer be required once metastases have been established. Our understanding of MMP pathophysiology in cancer has expanded considerably in the past 10 years. Current views indicate that: (1) most MMPs in tumors are made by stromal cells, not carcinoma cells; (2) cancer cells induce stromal cells to synthesize MMPs using extracellular matrix metalloproteinase inducer (EMMPRIN) and cytokine stimulatory mechanisms; and (3) MMPs promote cell migration and the release of growth factors sequestered in the extracellular matrix. MMPs have a dual function in tumor angiogenesis: MMP-2 and MT1-MMP are required in breaking down basement membrane barriers in the early stage of angiogenesis, while other MMPs are involved in the generation of an angiogenic inhibitor, angiostatin. In spite of considerable recent progress in identifying multiple roles of MMPs in disease, our understanding of MMP function in cancer is far from complete (see Table 1). Based on accumulated data, it is recommended that future MMPI trials focus on: (1) patients with early stage cancer; (2) the use of MMPIs along with chemotherapy; (3) the measurement of MMPs in tumor tissue and blood as a means of identifying patients who are more likely to respond to MMPI therapy; and (4) identification of biomarkers that reflect activation or inhibition of MMPs in vivo.read more
Citations
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Journal ArticleDOI
B7h Triggering Inhibits the Migration of Tumor Cell Lines
Chiara Dianzani,Rosalba Minelli,Casimiro Luca Gigliotti,Sergio Occhipinti,Mirella Giovarelli,Laura Conti,Elena Boggio,Yogesh Shivakumar,Gianluca Baldanzi,Valeria Malacarne,Elisabetta Orilieri,Giuseppe Cappellano,Roberto Fantozzi,Daniele Sblattero,Junji Yagi,José M. Rojo,Annalisa Chiocchetti,Umberto Dianzani +17 more
TL;DR: In this article, the effect of B7h triggering via a soluble form of ICOS (ICOS-Fc) inhibits the adhesion of polymorphonuclear and tumor cell lines to HUVECs.
Journal ArticleDOI
Importance of plasma matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinase (TIMP) in development of fibrosis in agnogenic myeloid metaplasia.
TL;DR: The literature shows that TIMP-1 (both the total, complex and the free form) is significantly increased in AMM and other myeloproliferative syndromes (including polycythemia vera (PV) and essential thrombocytosis (ET)), while MMP-3 is significantly decreased, and levels of Mmp-2 and M MP-9 are not different from control values.
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Blockade of Voltage-Gated Sodium Channels Inhibits Invasion of Endocrine-Resistant Breast Cancer Cells
TL;DR: The ion current and expression profile of VGSC in estrogen receptor (ER)-positive and silenced breast cancer cells and its possible influence on their proliferation, motility and invasion are examined to suggest Pharmacological or genetic blockade of Nav1.5 may serve as a potential anti-metastatic therapy for breast cancer.
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Metastasis-focused cell-based SELEX generates aptamers inhibiting cell migration and invasion.
Elina Zueva,Elina Zueva,Laila Illán Rubio,Laila Illán Rubio,Frédéric Ducongé,Frédéric Ducongé,Bertrand Tavitian,Bertrand Tavitian +7 more
TL;DR: A proof‐of‐concept study demonstrates the potential of cell‐based SELEX to yield ligands that selectively recognize aggressive metastatic cells and inhibit phenotypes linked to metastatic potential.
Journal ArticleDOI
Tissue inhibitor of metalloproteinase 1 expression associated with gene demethylation confers anoikis resistance in early phases of melanocyte malignant transformation.
Tatiana Iervolino Ricca,Gangning Liang,Ana Paula M. Suenaga,Sang Won Han,Peter A. Jones,Miriam Galvonas Jasiulionis +5 more
TL;DR: It is demonstrated for the first time an increment in Timp1 expression since the early phases of melanocyte malignant transformation, associated to a progressive gene demethylation, which confers anoikis resistance.
References
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Journal ArticleDOI
Matrix Metalloproteinases: A Review
Henning Birkedal-Hansen,William G. I. Moore,M.K. Bodden,L.J. Windsor,B. Birkedal-Hansen,Arthur A. Decarlo,Jeffrey A. Engler +6 more
TL;DR: The present review discusses in detail the primary structures and the overlapping yet distinct substrate specificities of MMPs as well as the mode of activation of the unique MMP precursors.
Journal ArticleDOI
A matrix metalloproteinase expressed on the surface of invasive tumour cells
Hiroshi Sato,Takahisa Takino,Yasunori Okada,Jian Cao,Akira Shinagawa,Etsuhide Yamamoto,Motoharu Seiki +6 more
TL;DR: The cloning of the complemen-tary DNA encoding a new matrix metalloproteinase with a potential transmembrane domain is reported, which may trigger invasion by tumour cells by activating pro-gelatinase A on the tumour cell surface.
Journal ArticleDOI
Molecular bases of the acute coronary syndromes
TL;DR: In the latter half of this century, the advent of coronary arteriography permitted definition in the living patient of coronary stenoses due to atherosclerosis, which allowed the development of rational treatment modalities such as coronary artery bypass surgery and percutaneous transluminal coronary angioplasty as discussed by the authors.
Journal ArticleDOI
Mechanism Of Cell Surface Activation Of 72-kDa Type IV Collagenase ISOLATION OF THE ACTIVATED FORM OF THE MEMBRANE METALLOPROTEASE
Alex Y. Strongin,Ivan E. Collier,Gregory A. Bannikov,Barry L. Marmer,Gregory A. Grant,Gregory I. Goldberg +5 more
TL;DR: Activation of 72T4Cl on the cell membrane provides a basic mechanism for spatially regulated extracellular proteolysis and presents a new target for prognosis and treatment of metastatic disease.
Journal ArticleDOI
Changing Views of the Role of Matrix Metalloproteinases in Metastasis
TL;DR: A new view of the functional role of M MPs in metastasis is presented, which suggests that MMPs are important in creating and maintaining an environment that supports the initiation and maintenance of growth of primary and metastatic tumors.
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