Membrane-type matrix metalloproteinases: expression, roles in metastatic prostate cancer progression and opportunities for drug targeting

The membrane-type matrix metalloproteinases(MT-MMPs),an important subgroup of the wider MMP family,demonstrate widespread expression in multiple tumor types,and play key roles in cancer growth,migration,invasion and metastasis.Despite a large body of published research,relatively little information exists regarding evidence for MT-MMP expression and function in metastatic prostate cancer.This review provides an appraisal of the literature describing gene and protein expression in prostate cancer cells and clinical tissue,summarises the evidence for roles in prostate cancer progression,and examines the data relating to MT-MMP function in the development of bone metastases.Finally,the therapeutic potential of targeting MT-MMPs is considered.While MT-MMP inhibition presents a significant challenge,utilisation of MT-MMP expression and proteolytic capacity in prostate tumors is an attractive drug development opportunity.

Construction of Antisense MT1-MMP Vector and Its Inhibitory Effects on Invasion of Human Ovarian Cancer Cells

Membrane-type 1 matrix metalloproteinase （MT1-MMP/MMP-14） plays crucial roles in tumor cell growth, invasion, and angiogenesis. To clarify whether the endogenously expressed MT1-MMP in metastatic human ovarian carcinoma cell lines SKOV3 plays a critical role in tumor cell invasiveness, antisense MT1-MMP cloned in eukaryotic expression vector pMMP14as was transferred into SKOV3 cells. 48h after transfection, decreased expression of endogenous MT1- MMP protein was detected in pMMP14as-transfected SKOV3 cells and the activation of pro-MMP2 was inhibited markedly. The mean percentage of invasive cells was （62. 50 ± 5. 30） % in pMMP14as-transfected cells, which was obviously less than that （97.20±6.90） % in the control. Thus, antisense MT1-MMP effectively inhibited the endogenous MT1-MMP expression and the invasiveness in SKOV3 cells, suggesting that MT1-MMP may be a therapeutic target molecule for human invaslve ovarian cancers.

Elliptical inclusion in an anisotropic plane:non-uniform interface effects

We study the plane deformation of an elastic composite system made up of an anisotropic elliptical inclusion and an anisotropic foreign matrix surrounding the inclusion.In order to capture the influence of interface energy on the local elastic field as the size of the inclusion approaches the nanoscale,we refer to the Gurtin-Murdoch model of interface elasticity to describe the inclusion-matrix interface as an imaginary and extremely stiff but zero-thickness layer of a finite stretching modulus.As opposed to isotropic cases in which the effects of interface elasticity are usually assumed to be uniform(described by a constant interface stretching modulus for the entire interface),the anisotropic case considered here necessitates non-uniform effects of interface elasticity(described by a non-constant interface stretching modulus),because the bulk surrounding the interface is anisotropic.To this end,we treat the interface stretching modulus of the anisotropic composite system as a variable on the interface curve depending on the specific tangential direction of the interface.We then devise a unified analytic procedure to determine the full stress field in the inclusion and matrix,which is applicable to the arbitrary orientation and aspect ratio of the inclusion,an arbitrarily variable interface modulus,and an arbitrary uniform external loading applied remotely.The non-uniform interface effects on the external loading-induced stress distribution near the interface are explored via a group of numerical examples.It is demonstrated that whether the nonuniformity of the interface effects has a significant effect on the stress field around the inclusion mainly depends on the direction of the external loading and the aspect ratio of the inclusion.

The role of MT1-MMP in the progression and metastasis of osteosarcoma

The dysregulation of Membrane-type 1 matrix metalloproteinase(MT1-MMP)has been extensively studied in numerous cancer types,and plays key roles in angiogenesis,cancer progression,and metastasis.MT1-MMP is a predictor of poor prognosis in osteosarcoma(OS),yet the molecular mechanisms of disease progression are unclear.This review provides a summary of the literature relating to the gene and protein expression of MT1-MMP(MMP-14)in OS clinical samples,evaluates the expression in cell lines and experimental models,and analyses its potential role in the progression and metastasis of OS.In addition,the therapeutic potential of MT1-MMP as a drug target has been assessed.Due to the biological complexity of MMPs,inhibition has proven to be challenging.However,exploiting the expression and proteolytic capacity of MT1-MMP could open new avenues in the search for novel,safer and selective drugs for use in OS.