Role of Matrix Metalloproteinases and Plasminogen Activators in Cancer Invasion and Metastasis: Therapeutic Strategies

Zucker, Stanley; Cao, Jian; Molloy, Christopher J.

doi:10.1016/b978-012072651-6/50007-3

Cited by 10 publications

(4 citation statements)

References 156 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well known that cancer progression and metastasis require cell motility, entry into the blood (or lymphatic) stream followed by exit, breakdown of extracellular matrix, and growth in a "fertile" environment, supported by neo-angiogenesis. Given the multiplicity of pathways involved in cancer progression, increasing attention is being paid to targeting these pathways with noncytotoxic drugs, alone or in combination with cytotoxic agents (2,3). Two of the major target pathways supporting tumor growth and metastasis are neo-angiogenesis (4 -8) and matrix breakdown by matrix metalloproteinases (MMPs) (3, 6, 9 -12).…”

mentioning

confidence: 99%

Rho kinase and matrix metalloproteinase inhibitors cooperate to inhibit angiogenesis and growth of human prostate cancer xenotransplants

Somlyo¹,

Phelps²,

diPierro³

et al. 2003

FASEB j.

View full text Add to dashboard Cite

The purpose of this study was to determine the effects of inhibitors of Rho kinase (ROK) and matrix metalloproteinases (MMPs) on angiogenesis and tumor growth and to evaluate ROK activity in human prostate cancer PC3 cells and endothelial cells (HUVECs). Vacuolation by endothelial cells and lumen formation, the earliest detectable stages of angiogenesis, were inhibited by the ROK inhibitor Wf-536. Combining Wf-536 with the MMP inhibitor Marimastat greatly enhanced in vitro inhibition of endothelial vacuolation, lumen and cord formation, and VEGF- and HGF-stimulated endothelial sprout formation from aorta. Inhibition of sprout formation by the two inhibitors was synergistic. Both agents inhibited migration of HUVECs. The regulatory subunit (MYPT1) of the myosin phosphatase was phosphorylated in PC3 cells and HUVECs, and phosphorylation of MYPT1 and the myosin regulatory light chain was reduced by Wf-536, providing direct evidence of ROK activity. Early treatment of immuno-incompetent mice bearing xenotransplants of PC3 cells with a combination of Wf-536 plus Marimastat with or without Paclitaxel, significantly inhibited tumor growth, prevented tumor growth escape after discontinuation of Paclitaxel, and increased survival.

show abstract

mentioning

confidence: 99%

Rho kinase and matrix metalloproteinase inhibitors cooperate to inhibit angiogenesis and growth of human prostate cancer xenotransplants

Somlyo¹,

Phelps²,

diPierro³

et al. 2003

FASEB j.

View full text Add to dashboard Cite

show abstract

“…Pre-clinical data have demonstrated that interfering with MMP expression inhibits the metastatic and tumor growth, including in a breast cancer model [161]. This has led to the development of a number of MMP inhibitors, such as batimastat and marimastat, which are low-molecular-weight peptidomimetic inhibitors [162]. Unfortunately, these early preclinical studies were not repeated in clinical trials, as a phase 3 trial with marimastat showed no effect in prolonging progression-free survival when used after first-line chemotherapy for metastatic breast cancer [163].…”

Section: Targeting Tumors' Ability To Induce Angiogenesismentioning

confidence: 99%

Antitumor Drugs and Their Targets

Dembić

2020

Molecules

View full text Add to dashboard Cite

Through novel methodologies, including both basic and clinical research, progress has been made in the therapy of solid cancer. Recent innovations in anticancer therapies, including immune checkpoint inhibitor biologics, therapeutic vaccines, small drugs, and CAR-T cell injections, mark a new epoch in cancer research, already known for faster (epi-)genomics, transcriptomics, and proteomics. As the long-sought after personalization of cancer therapies comes to fruition, the need to evaluate all current therapeutic possibilities and select the best for each patient is of paramount importance. This is a novel task for medical care that deserves prominence in therapeutic considerations in the future. This is because cancer is a complex genetic disease. In its deadly form, metastatic cancer, it includes altered genes (and their regulators) that encode ten hallmarks of cancer-independent growth, dodging apoptosis, immortalization, multidrug resistance, neovascularization, invasiveness, genome instability, inflammation, deregulation of metabolism, and avoidance of destruction by the immune system. These factors have been known targets for many anticancer drugs and treatments, and their modulation is a therapeutic goal, with the hope of rendering solid cancer a chronic rather than deadly disease. In this article, the current therapeutic arsenal against cancers is reviewed with a focus on immunotherapies.

show abstract

“…MMP activity is tightly controlled through several different mechanisms. In general, MMPs are expressed in very low amounts, and their transcription is regulated either positively or negatively by oncogenes, cytokines, and growth factors (Sternlicht et al 1999;Zucker et al 2002). Cell-cell and cell-matrix interactions may also affect MMP gene expression (Hidalgo and Eckhardt, 2001).…”

Section: Chemokines and Mmps In Colorectal Cancermentioning

confidence: 99%

“…Certain MMPs that contain furin-like recognition domains in their propeptides (MMP-11, MT-MMPs, MMP-28) can be activated intracellularly by members of the subtilisin family of serine proteases. Extracellular activation of MMPs can be mediated by proteolytic cleavage of the pro-domain by serine proteases, such as plasmin, or by other active MMPs (Sato et al 1994;Zucker et al 2002). For example, active MMP-3 is capable of activating proMMP-9 and proMMP-1.…”

Section: Chemokines and Mmps In Colorectal Cancermentioning

confidence: 99%