Biomedical subjects

J M Foidart

Publications and source records attributed to J M Foidart.

At least 37 records · Page 2Linked to original sources

PubMed2003

[Benefits and limitations of mammography].

The literature on screening mammography provides ample opportunity for doubt (the sceptics) and dogma (the screening zealots), and can be interpreted to prove both benefit and harm. The benefit of mammography screening, if any, is modest and the balance between beneficial (potentially, a 20% relative reduction in breast cancer mortality with no significant benefit on all-cause mortality) and harmful (physical and psychological morbidity related to the 15-40% missed cancers and the 80-90% false-positive diagnoses) effects is still delicate. The mammogram alone is a modest weapon. Concurrent clinical breast examination is mandatory. Women that are concerned about breast cancer should be fully informed of the potential benefits and risks of screening mammography. These women should benefit from mammography with concurrent clinical breast examination, and possible whole-breast ultrasound in heterogeneously dense and extremely dense breast patterns.

Age Factors↗

PubMed2003

[Hormone replacement therapy one year after the results of the Women's Health Initiative].

The currently reported data concerning the large WHI randomized controlled trial compare the impact of continuous combined conjugated estrogens + medroxyprogesterone acetate vs placebo in postmenopausal women. These results appear largely pessimistic. After 5.2 years of hormone replacement, an excess of coronary heart disease, cerebrovascular disease, venous thromboembolism, breast cancer incidence and extension, mild cognitive impairment and dementia is recorded. By contrast, osteoporotic fracture risk and colorectal cancer are decreased during hormone replacement. Accordingly, this hormonal treatment can no longer be recommended on a long term basis, except after extensive risk-benefit balance evaluation. It should no longer be prescribed for prevention of chronic diseases. It remains indicated during 4-5 years for relief of vasomotor symptoms, genital atrophy and, potentially, for some aspects of quality of life. HRT should probably be prescribed in minimal-effective dosages; new regimens, routes of administration, new compounds and associations should be envisaged in order to avoid cardiovascular or breast problems. However these new approaches ask for thorough validation studies.

Estrogen Replacement Therapy↗

PubMed2003

Pathogenic role of matrix metalloproteases and their inhibitors in asthma and chronic obstructive pulmonary disease and therapeutic relevance of matrix metalloproteases inhibitors.

Matrix metalloproteinases (MMPs) are an at least 23 member family of calcium and zinc dependent enzymes implicated in many physiological and pathological processes. Asthma, chronic obstructive pulmonary disease (COPD) and emphysema are diseases associated with an inflammation of the airways and lung parenchyma. In this review, we focus on the role played by MMPs in the pathogenesis of inflammation, airway remodelling and alveolar destruction, depicting the observational studies in humans and the experimental studies in animal models. During the course of asthma, MMP-2,-8,-9 and TIMP-1 are expressed at baseline and the allergen exposure or exacerbations of the disease lead to an increase of MMP-9 secretion being at this time much higher than that of TIMP-1, allowing temporarily a matrix damage, possibly followed by abnormal repair. Animal models suggest a predominant role for MMP-9 and MMP-12 in the pathogenesis of pulmonary inflammation and link an absence of MMP-2 to an increased parenchymal inflammation. In COPD and emphysema, human studies indicate an over-secretion of MMP-2,-8,-9 and animal models pointout MMP-1 and MMP-12 as being key players in the pathogenesis of emphysema. Taken together, these data identify specific MMP inhibition as appropriate target for therapeutic intervention in asthma or COPD/emphysema They also strongly argue against the widespread use of large spectrum non specific inhibitors that could be detrimental.

Animals↗

PubMed2003

[Anemia associated with malaria and intestinal helminthiasis in Lubumbashi].

The purpose of this study is to evaluate and determine the prevalence of anemia and associated factors (malaria and intestinal helminthiasis) in some high risk groups, especially in pregnant and breast-feeding women and in children aged 1-2 years old from within a deprived semi-urban population of Lubumbashi (Bongonga and Sendwe). These results were compared to those obtained from an urban population having a more satisfying socio-economic situation (University Clinics). The overall frequency of anemia in the subjects studied from the three centres varies from 50-80%. The proportion of anemic cases is clearly higher in the Bongonga and Sendwe populations (70-80%) than in that of the urban group (50%) (P < 0.05). Among all of the subjects examined, pregnant women are found to be the group with the highest proportion of anemic patients (P < 0.05). All things considered, anemia is associated with malaria in 40% of the cases and with intestinal parasitism (Ascaris and/or Ankylostome infestation) in 9%. Faced with such a situation, the strategy to fight against anemia and associated parasitosis demands and requires multi-disciplinary actions centred on health education, collective screening and specific anti-parasite treatment.

Adult↗

PubMed2002

Percutaneous stereotactic en bloc excision of nonpalpable breast carcinoma: a step in the direction of supraconservative surgery.

Recently, the advanced breast biopsy instrumentation (ABBI) system has been introduced as an alternative to conventional breast biopsy techniques. This study was prospectively conducted to evaluate the potential of the ABBI method in locoregional management of a consecutive series of patients with nonpalpable mammographically detected breast carcinomas. Sixty-one consecutive patients underwent an ABBI procedure as a first step before possible surgery for nonpalpable breast lesions that would in any case require complete excision. For the 27 patients in whom the ABBI biopsy revealed malignancy further surgery was recommended, including re-excision of the biopsy site and axillary dissection in cases of infiltrating carcinoma. We calculated the probabilities that the ABBI specimen would have tumor-free margins and that a definitely complete excision had been achieved as a function of the mammographic or pathological diameter of the cancer. For cancer with a pathological diameter less than 10 mm measured on the ABBI specimen, the probability (92%) of obtaining complete resection was significantly better than for larger lesions (P=0.01, Fisher's exact test). Although the therapeutic perspectives for the ABBI method are limited at present, we suggest that this approach is a first step in the direction of a surgical strategy that is better adapted to the pathological characteristics peculiar to these small tumors, whose incidence is increasing.

Journal Article↗

PubMed2002

MT1-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression.

Membrane type 1 metalloprotease (MT1-MMP) is a transmembrane metalloprotease that plays a major role in the extracellular matrix remodeling, directly by degrading several of its components and indirectly by activating pro-MMP2. We investigated the effects of MT1-MMP overexpression on in vitro and in vivo properties of human breast adenocarcinoma MCF7 cells, which do not express MT1-MMP or MMP-2. MT1-MMP and MMP-2 cDNAs were either transfected alone or cotransfected. All clones overexpressing MT1-MMP 1) were able to activate endogenous or exogenous pro-MMP-2, 2) displayed an enhanced in vitro invasiveness through matrigel-coated filters independent of MMP-2 transfection, 3) induced the rapid development of highly vascularized tumors when injected subcutaneously in nude mice, and 4) promoted blood vessels sprouting in the rat aortic ring assay. These effects were observed in all clones overexpressing MT1-MMP regardless of MMP-2 expression levels, suggesting that the production of MMP-2 by tumor cells themselves does not play a critical role in these events. The angiogenic phenotype of MT1-MMP-producing cells was associated with an up-regulation of VEGF expression. These results emphasize the importance of MT1-MMP during tumor angiogenesis and open new opportunities for the development of anti-angiogenic strategies combining inhibitors of MT1-MMP and VEGF antagonists.

Animals↗

PubMed2002

[Clinical study of the month. Benefit/risk balance of postmenopausal estrogen-progestin treatment in peril in the Women's Health Initiative study: practical attitude of the clinician].

The Women's Health Initiative (WHI) is sponsored by the NIH. The study focuses on risk and benefits of strategies that could potentially reduce the incidence of heart disease, breast and colon cancer, and fractures in postmenopausal women. One arm of the study, a double-blind, placebo-controlled trial, looking at the effects of continuous combined estrogen-progestin regimen was stopped prematurely based on health risks which exceeded health benefits. The main reason for this decision was the increase in risk of invasive breast cancer, as well as a slight increase in the rate of myocardial infarction and stroke. In this paper, we inform our colleagues of the detailed results of the study. We comment on its limitation and discuss the new original observations. Finally, we integrate the others to previous world literature data that are confirmed by the WHI study. It is important for the individual prescribing practitioner to issue practical conclusions and therapeutic recommendations. The department of Obstetrics and Gynaecologic of the University of Liege, in agreement with the European Menopause Society and the International Menopause Society, is convinced that there is no alternative to the hormone replacement therapy for menopausal symptoms. We should stick to the traditional indications for hormones, namely vasomotor symptoms and osteoporosis. We should continue to recommend hormones for symptomatic women. One should realize that the risk for breast cancer appears only after several years of use, and the risk for cardiovascular events below age 60 is very small (the age of the patients was 63 at inclusion in the WHI study). We should encourage women to take the necessary measures for routine, periodic breast examinations (both manual, echographic and radiographic). Women who use HRT for more than 5 years should discuss the latest data of the WHI study with their physician, in order to consider their individual benefit-risk equation. Those who feel good on hormones and are fully satisfied with this treatment should learn of possible harm after long-term use. It is important to take into account the importance of quality of life. We should leave to the patient the final decision whether or not to continue the treatment. It is presently impossible to decide whether other estroprogestin associations, other administration routes and other molecules such as estradiol, natural progesterone or other progestins, SERMS and Tibolone could have an impact very different from that of the estroprogestin combination used in the WHI study. It is the duty of every physician to decide, from the complex epidemiological data obtained in the aged women (63-68 years) with a high cardiovascular risk in the WHI study, if it is possible or not in each individual case to recommend the initiation or pursue of an hormone replacement therapy.

Age Factors↗

PubMed2001

Induction of SPARC by VEGF in human vascular endothelial cells.

SPARC/osteonectin/BM-40 is a matricellular protein that is thought to be involved in angiogenesis and endothelial barrier function. Previously, we have detected high levels of SPARC expression in endothelial cells (ECs) adjacent to carcinomas of kidney and tongue. Although SPARC-derived peptide showed an angiogenic effect, intact SPARC itself inhibited the mitogenic activity of vascular endothelial growth factor (VEGF) for ECs by the inhibiting phosphorylation of flt-1 (VEGF receptor 1) and subsequent ERK activation. Thus, the role of SPARC in tumor angiogenesis, stimulation or inhibition, is still unclear. To clarify the role of SPARC in tumor growth and progression, we determined the effect of VEGF on the expression of SPARC in human microvascular EC line, HMEC-1, and human umbilical vein ECs. VEGF increased the levels of SPARC protein and steady-state levels of SPARC mRNA in serum-starved HMEC-1 cells. Inhibitors (SB202190 and SB203580) of p38, a mitogen-activated protein (MAP) kinase, attenuated VEGF-stimulated SPARC production in ECs. Since intact SPARC inhibits phosphorylation ERK MAP kinase in VEGF signaling, it was suggested that SPARC plays a dual role in the VEGF functions, tumor angiogenesis, and extravasation of tumors mediated by the increased permeability of endothelial barrier function.

Cells, Cultured↗

PubMed2001

Down-regulation of vascular endothelial growth factor by tissue inhibitor of metalloproteinase-2: effect on in vivo mammary tumor growth and angiogenesis.

The tissue inhibitor of metalloproteinases-2 (TIMP-2) has at least two independent functions, i.e., regulation of matrix metalloproteinases and growth promoting activity. We investigated the effects of TIMP-2 overexpression, induced by retroviral mediated gene transfer, on the in vivo development of mammary tumors in syngeneic mice inoculated with EF43.fgf-4 cells. The EF43.fgf-4 cells established by stably infecting the normal mouse mammary EF43 cells with a retroviral expression vector for the fgf-4 oncogene, are highly tumorigenic and overproduce vascular endothelial growth factor (VEGF). Despite a promotion of the in vitro growth rate of EF43.fgf-4 cells overexpressing timp-2, the in vivo tumor growth was delayed. At day 17 post-cell injection, the volume of tumor derived from TIMP-2-overexpressing cells was reduced by 80% as compared with that obtained with control cells. Overexpression of TIMP-2 was associated with a down-regulation of VEGF expression in vitro and in vivo, a reduction of vessel size, density, and blood supply in the induced tumors. In addition, TIMP-2 completely inhibited the angiogenic activity of EF43.fgf-4 cell-conditioned medium in vitro using a rat aortic ring model. Our findings suggest that overexpression of TIMP-2 delays growth and angiogenesis of mammary carcinoma in vivo and that down-regulation of VEGF expression may play an important role in this TIMP-2-mediated antitumoral and antiangiogenic effects. Finally the in vivo delivery of TIMP-2, as assessed by i.v. injection of recombinant adenoviruses vectors, significantly reduced the growth of the EF43.fgf-4-induced tumors. This effect of TIMP-2 was shown to be equally comparable with that of angiostatin, a known potent inhibitor of angiogenesis.

Adenoviridae↗

PubMed2001

The plasminogen activator inhibitor PAI-1 controls in vivo tumor vascularization by interaction with proteases, not vitronectin. Implications for antiangiogenic strategies.

The plasminogen (Plg)/plasminogen activator (PA) system plays a key role in cancer progression, presumably via mediating extracellular matrix degradation and tumor cell migration. Consequently, urokinase-type PA (uPA)/plasmin antagonists are currently being developed for suppression of tumor growth and angiogenesis. Paradoxically, however, high levels of PA inhibitor 1 (PAI-1) are predictive of a poor prognosis for survival of patients with cancer. We demonstrated previously that PAI-1 promoted tumor angiogenesis, but by an unresolved mechanism. We anticipated that PAI-1 facilitated endothelial cell migration via its known interaction with vitronectin (VN) and integrins. However, using adenoviral gene transfer of PAI-1 mutants, we observed that PAI-1 promoted tumor angiogenesis, not by interacting with VN, but rather by inhibiting proteolytic activity, suggesting that excessive plasmin proteolysis prevents assembly of tumor vessels. Single deficiency of uPA, tissue-type PA (tPA), uPA receptor, or VN, as well as combined deficiencies of uPA and tPA did not impair tumor angiogenesis, whereas lack of Plg reduced it. Overall, these data indicate that plasmin proteolysis, even though essential, must be tightly controlled during tumor angiogenesis, probably to allow vessel stabilization and maturation. These data provide insights into the clinical paradox whereby PAI-1 promotes tumor progression and warrant against the uncontrolled use of uPA/plasmin antagonists as tumor angiogenesis inhibitors.

Angiogenesis Inhibitors↗

PubMed2001

Fetal renal hyperechogenicity in intrauterine growth retardation: importance and outcome.

The object of the study was to investigate the outcome in growth-retarded newborns who were diagnosed with fetal renal hyperechogenicity without anatomical abnormality during any stage of pregnancy. Depending on the fetal renal ultrasonography result, the cases were divided into two study groups. There was an intrauterine growth-retarded group with fetal renal medullary hyperechogenicity and another group without fetal renal medullary hyperechogenicity. The renal parenchyma was observed after birth, within the first 5 days of life, and several times until the 14th postpartum day in positive cases. Hyperechogenic renal medullae were detected in 25 of 90 cases with intrauterine growth retardation during the 8-month study period. This may be an in utero cause of subsequent intrauterine and neonatal complications, such as cesarean section because of fetal distress (36%), perinatal infection (24%), treatment in a neonatal intensive care unit (52%), or increased perinatal mortality (8%). The results demonstrate that fetuses with hyperechoic medullae had 1.5 times the risk of an abnormal outcome compared with fetuses with normal echoic kidneys and intrauterine growth retardation. Detailed ultrasound examinations of renal parenchyma appear to be useful for the prenatal diagnosis of intrauterine hypoxia, allowing the detection of possible pathological fetal conditions in utero.

Adult↗

PubMed2001

Improved quantification of angiogenesis in the rat aortic ring assay.

In vitro angiogenesis assays are essential for the identification of potential angiogenic agents and screening for pharmacological inhibitors. Among these assays, the rat aortic ring model developed by Nicosia bridges the gap between in vivo and in vitro models. The quantification of angiogenesis on this system must be applicable to characterise vascular networks of various states of complexity. We present here an improved computer-assisted image analysis which allows: (1) the determination of the aortic ring area and its factor shape; (2) the number of microvessels, the total number of branchings, the maximal microvessel length and the microvessel distribution; (3) the total number of isolated fibroblast-like cells and their distribution. We show that this method is suitable to quantify spontaneous angiogenesis as well as to analyse a complex microvascular network induced by various concentrations of vascular endothelial growth factor (VEGF). In addition, by evaluating a new parameter, the fibroblast-like cell distribution, our results show that: (1) during spontaneous angiogenic response, maximal fibroblast-like cell migration delimits microvascular outgrowth; and (2) the known angiogenic inhibitor Batimastat prevents endothelial cell sprouting without completely blocking fibroblast-like cell migration. Finally, this new method of quantification is of great interest to better understand angiogenesis and to test pro- or anti-angiogenic agents.

Animals↗

PubMed2001

Matrix metalloproteinases and TIMP-1 production by peripheral blood granulocytes from COPD patients and asthmatics.

Both asthmatic and COPD patients were found to have increased amounts of granulocytes and matrix metalloproteinase-9 (MMP-9) in their sputum. The present study was conducted to investigate whether the elevated amounts of MMP-9 and TIMP-1 found in such patients' airways may be linked to an enhanced secretion by granulocytes. Blood granulocytes from asthmatics (n = 10), COPD patients (n = 11), and healthy controls (n = 11) were isolated and cultured under basal conditions or after stimulation by phorbol 12-myristate 13-acetate (PMA) or N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). MMP-9 activity was detected by zymography while MMP-8 and TIMP-1 levels were measured by ELISA. In zymography, pro- and activated forms of MMP-9 were present in each group (healthy subjects, asthmatics, and COPD patients). Spontaneous release was not different between the three groups. Stimulation by fMLP and PMA increased to a similar extent the release of MMP-9 by granulocytes in all the three groups. TIMP-1 levels were also increased after stimulation by PMA and fMLP only in healthy subjects and COPD patients. MMP-8 levels were barely detectable. We conclude that circulating granulocytes from COPD patients and asthmatics do not display an abnormal secretion of MMP-9, and that granulocytes from asthmatics have an impaired ability to release TIMP-1 upon stimulation.

Adult↗

PubMed2001

Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions.

Vascular endothelial growth factor (VEGF) stimulates angiogenesis by activating VEGF receptor-2 (VEGFR-2). The role of its homolog, placental growth factor (PlGF), remains unknown. Both VEGF and PlGF bind to VEGF receptor-1 (VEGFR-1), but it is unknown whether VEGFR-1, which exists as a soluble or a membrane-bound type, is an inert decoy or a signaling receptor for PlGF during angiogenesis. Here, we report that embryonic angiogenesis in mice was not affected by deficiency of PlGF (Pgf-/-). VEGF-B, another ligand of VEGFR-1, did not rescue development in Pgf-/- mice. However, loss of PlGF impaired angiogenesis, plasma extravasation and collateral growth during ischemia, inflammation, wound healing and cancer. Transplantation of wild-type bone marrow rescued the impaired angiogenesis and collateral growth in Pgf-/- mice, indicating that PlGF might have contributed to vessel growth in the adult by mobilizing bone-marrow-derived cells. The synergism between PlGF and VEGF was specific, as PlGF deficiency impaired the response to VEGF, but not to bFGF or histamine. VEGFR-1 was activated by PlGF, given that anti-VEGFR-1 antibodies and a Src-kinase inhibitor blocked the endothelial response to PlGF or VEGF/PlGF. By upregulating PlGF and the signaling subtype of VEGFR-1, endothelial cells amplify their responsiveness to VEGF during the 'angiogenic switch' in many pathological disorders.

Animals↗

PubMed2001

Down-Regulation of MT1-MMP expression by the alpha3 chain of type IV collagen inhibits bronchial tumor cell line invasion.

The basement membrane (BM) is the first barrier encountered by tumor cells when they become invasive. Moreover, some invasive tumor clusters are surrounded by a remnant or neosynthetized BM material. We have previously reported the presence of a particular alpha chain of type IV collagen, the alpha3(IV) chain, in bronchopulmonary carcinomas. This chain was not detected in the normal bronchial epithelium, but was found around some invasive tumor cluster BM. In the present study, we examined the effects of the alpha3(IV) chain on the invasive properties of bronchial tumor cell lines, with special emphasis on their expression of matrix metalloproteinase-2 (MMP-2) and its activator, membrane type 1-matrix metalloproteinase (MT1-MMP), which is largely involved in tumor progression. Two epithelial bronchial cell lines (16HBE14o- and BZR), showing different invasive abilities, were evaluated. Using the Boyden chamber invasion assay, we demonstrated that the alpha3(IV) chain inhibits the invasive properties of BZR cells and modifies their morphology by inducing an epithelial cell shape. In the presence of the recombinant NC1 domain of the alpha3(IV) chain, the expression of MMP-2 and tissue inhibitor of metalloproteinase-2 (TIMP-2) was not modified in either cell line. The NC1 alpha3(IV) domain did not modulate the MT1-MMP expression of noninvasive 16HBE14o- cells, whereas a 50% decrease of MT1-MMP mRNA was observed in invasive BZR cells. Accordingly, Western blot analyses showed a disappearance of the 45-kd MT1-MMP form when BZR cells were treated with the recombinant NC1 alpha3(IV) domain. These findings suggest that the alpha3 chain of type IV collagen may play a role in tumor invasion, at least by decreasing the expression and synthesis of MT1-MMP.

Bronchi↗

PubMed2001

Influence of plasminogen activator inhibitor type 1 on choroidal neovascularization.

High levels of the plasminogen activators, but also their inhibitor, plasminogen activator inhibitor 1 (PAI-1), have been documented in neovascularization of severe ocular pathologies such as diabetic retinopathy or age-related macular degeneration (AMD). AMD is the primary cause of irreversible photoreceptors loss, and current therapies are limited. PAI-1 has recently been shown to be essential for tumoral angiogenesis. We report here that deficient PAI-1 expression in mice prevented the development of subretinal choroidal angiogenesis induced by laser photocoagulation. When systemic and local PAI-1 expression was achieved by intravenous injection of a replication-defective adenoviral vector expressing human PAI-1 cDNA, the wild-type pattern of choroidal angiogenesis was restored. These observations demonstrate the proangiogenic activity of PAI-1 not only in tumoral models, but also in choroidal experimental neovascularization sharing similarities with human AMD. They identify therefore PAI-1 as a potential target for therapeutic ocular anti-angiogenic strategies.

Adenoviridae↗

PubMed2001

Presence of oestrogen receptor type beta in human retina.

BACKGROUND/AIMS: Recent studies have demonstrated the existence of two oestrogen receptor subtypes alpha (ORalpha) and beta (ORbeta) with significant differences of expression among organs. Since important pathologies of human eye could be linked to hormonal status, the expression of ORbeta in ocular posterior segment was sought. METHODS: Immunohistochemical localisation of ORbeta and ORalpha protein and detection of OR mRNAs by reverse transcription-polymerase chain reaction (RT-PCR) were performed in macular and extramacular regions of the retina and in the choroid on male and female donors eyes. RESULTS: ORbeta protein was localised in the ganglion cell layer and in the choroid. At the transcriptional level, mRNA for ORbeta and for ORalpha were both present. Local differences in the expression level were observed, however, suggesting the possibility of variation in the ratio of ORalpha v ORbeta. CONCLUSIONS: The coexistence of two oestrogen receptor subtypes in the human ocular posterior segment raises acute questions about their potential physiological role, but offers a perspective for preferential targeting of a specific receptor subtype.

Aged↗

PubMed2001

Contribution of MT1-MMP and of human laminin-5 gamma2 chain degradation to mammary epithelial cell migration.

Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a membrane-anchored matrix metalloproteinase (MMP) that is frequently associated with processes involving tissue remodelling and cell migration. We have examined MT1-MMP expression and subcellular distribution as a function of MCF10A mammary epithelial cell migration using an in vitro outgrowth migration assay. Stronger expression of MT1-MMP was observed at the mRNA and at the protein level in cells at the periphery of the outgrowth. As shown by videomicroscopy, these cells were involved in an orientated cell migration, in contrast to stationary cells distant from the periphery. Furthermore, MT1-MMP was mainly distributed in lamellipodia of migratory cells, as well as at their basal surface in contact with the substrate. Laminin-5 (Ln-5), a recently described substrate for MT1-MMP, was deposited preferentially in the matrix by migratory cells. Fragments of the gamma2 subunit of Ln-5 were also identified in migratory cultures of MCF10A cells, attesting to its proteolytic degradation. These fragments corresponded in size to those we observed after incubation of purified human Ln-5 with the recombinant catalytic domain of human MT1-MMP. We also show that anti-Ln5 blocking antibodies, MMP inhibitors (BB94 and TIMP-2) and MT1-MMP antisense oligonucleotides significantly decreased MCF10A cell migration. Taken together, these observations demonstrate that MT1-MMP is spatially and temporally regulated during MCF10A cell migration, and suggest that MT1-MMP-mediated pericellular proteolysis of Ln-5 gamma2 chain could contribute to this process.

Blotting, Western↗