Article

Unraveling the role of proteases in cancer.

Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA.
Clinica Chimica Acta (Impact Factor: 2.85). 03/2000; 291(2):113-35. DOI: 10.1016/S0009-8981(99)00224-7
Source: PubMed

ABSTRACT Investigators have been studying the expression and activity of proteases in the final steps of tumor progression, invasion and metastasis, for the past 30 years. Recent studies, however, indicate that proteases are involved earlier in progression, e.g., in tumor growth both at the primary and metastatic sites. Extracellular proteases may co-operatively influence matrix degradation and tumor cell invasion through proteolytic cascades, with individual proteases having distinct roles in tumor growth, invasion, migration and angiogenesis. In this review, we use cathepsin B as an example to examine the involvement of proteases in tumor progression and metastasis. We discuss the effect of interactions among tumor cells, stromal cells, and the extracellular matrix on the regulation of protease expression. Further elucidation of the role of proteases in cancer will allow us to design more effective inhibitors and novel protease-based drugs for clinical use.

0 Bookmarks
 · 
82 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Intravital imaging has provided molecular, cellular and anatomical insight into the study of tumor. Early detection and treatment of gastrointestinal (GI) diseases can be enhanced with specific molecular markers and endoscopic imaging modalities. We present a wide-field multi-channel fluorescence endoscope to screen GI tract for colon cancer using multiple molecular probes targeting matrix metalloproteinases (MMP) conjugated with quantum dots (QD) in AOM/DSS mouse model. MMP9 and MMP14 antibody (Ab)-QD conjugates demonstrate specific binding to colonic adenoma. The average target-to-background (T/B) ratios are 2.10 ± 0.28 and 1.78 ± 0.18 for MMP14 Ab-QD and MMP9 Ab-QD, respectively. The overlap between the two molecular probes is 67.7 ± 8.4%. The presence of false negative indicates that even more number of targeting could increase the sensitivity of overall detection given heterogeneous molecular expression in tumors. Our approach indicates potential for the screening of small or flat lesions that are precancerous.
    Biomedical Optics Express 05/2014; 5(5):1677-89. · 3.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Polymeric nanocarriers conjugated with low molecular weight drugs are designed in order to improve their efficacy and toxicity profile. This approach is particularly beneficial for anticancer drugs, where the polymer-drug conjugates selectively accumulate at the tumor site, due to the enhanced permeability and retention (EPR) effect. The conjugated drug is typically inactive, and upon its pH- or enzymatically- triggered release from the carrier, it regains its therapeutic activity. These settings lack information regarding drug-release time, kinetics and location. Thereby, real-time non-invasive intravital monitoring of drug release is required for theranostics (therapy and diagnostics). We present here the design, synthesis and characterization of a theranostic nanomedicine based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer owing its fluorescence-based monitoring of site-specific drug release to a self-quenched near-infrared fluorescence (NIRF) probe. We designed two HPMA copolymer-based systems that complement to a theranostic nanomedicine. The diagnostics system consists of self-quenched Cy5 (SQ-Cy5) as a reporter probe and the therapeutic system is based on the anticancer agent paclitaxel (PTX). HPMA copolymer-PTX/SQ-Cy5 systems enable site-specific release upon enzymatic degradation in cathepsin B-overexpressing breast cancer cells. The release of the drug occurs concomitantly with the activation of the fluorophore to its Turn-ON state. HPMA copolymer- SQ-Cy5 exhibit preferable body distribution and drug release compared with the free drug and probe when administered to cathepsin B-overexpressing 4T1 murine mammary adenocarcinoma-bearing mice. This approach of co-delivery of two complementary systems serves as a proof-of-concept for real-time deep tissue intravital orthotopic monitoring and may have the potential use in clinical utility as a theranostic nanomedicine.
    Cancer letters 03/2014; · 4.86 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We report the synthesis and application of novel graphene oxide and carbon nanotube oxide (GCN-O) composite. First, pristine multi-walled carbon nanotube was prepared by chemical vapour deposition furnace and then exfoliated and oxidised simultaneously by oxygen plasma etching. The superficial and volumetric compositions of GCN-O were measured by XPS spectroscopy and EDX spectroscopy, respectively. Both XPS and EDX analyses evidence that the GCN-O is composed of up to 20% of oxygen atoms. As a result, GCN-O forms a stable colloidal aqueous solution and shows to have strong interaction with the cell membrane of Tritrichomonas foetus protozoa, making easy its application as a drug carrier. Trichomoniasis infection of cattle is a devastating disease for cattle producers, causing some damages to females and fetus, and the abortion is the most serious result of this disease. There is no effective treatment for trichomoniasis infection yet. Therefore, new treatment, especially one with no collateral effects in animals, is required. With this goal in mind, our results suggest that water dispersible composite is a novel nanomaterial, promising for Trichomoniasis infection treatment and as therapeutic delivery agent as well.
    Materials Science and Engineering C 04/2014; · 2.40 Impact Factor

Full-text (2 Sources)

View
92 Downloads
Available from
Jun 4, 2014