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J M Foidart

Publications and source records attributed to J M Foidart.

At least 163 records · Page 9Linked to original sources

Basement membrane components (matrigel) promote the tumorigenicity of human breast adenocarcinoma MCF7 cells and provide an in vivo model to assess the responsiveness of cells to estrogen.

The ability to transplant human tumors into athymic nude mice allows studies of tumor cells in vivo. However, after s.c. injection the incidence of tumor and metastases in nude mice is frequently low. We have studied the tumorigenicity in nude mice of estradiol (E2)-sensitive breast adenocarcinoma MCF7 cells. Matrigel, an extract of basement membrane proteins, induces rapid tumor development after s.c. injection of MCF7 cells. In the absence of this matrice, MCF7 cells failed to induce tumor growth. In this in vivo model, MCF7 cells were analysed for their E2 sensitivity. Two weeks after inoculation in the presence of matrigel, cells formed growing tumors in intact mice supplemented with E2. In ovariectomized or untreated mice, tumor appearance was delayed and the growth level was very low. Thus, MCF7 cells formed tumors in the absence of E2 but retained in vivo their responsiveness to estrogen. Growing human tumors in nude mice provides a rapid and useful model for testing the sensitivity of cells to hormone.

Adenocarcinoma↗

Modulation of collagen and fibronectin synthesis in fibroblasts by normal and malignant cells.

The influence of various normal and malignant human cells on the level of collagen synthesis by human fibroblasts was tested in coculture. As revealed by immunoperoxidase staining, in cocultures with breast adenocarcinoma cells (MCF7, SA52, T47D) fibroblasts synthesized collagen while tumor cells did not. Fibroblasts displayed increased collagen production without change in the overall protein synthesis. Several other types of cells derived from normal human tissues (keratinocytes, normal mammary cells) or from fibrosarcoma, melanoma, cervical carcinoma, choriocarcinoma, or other breast adenocarcinoma (SW613, MDA, BT20) did not affect collagen synthesis of fibroblasts. Although to a lesser extent, this stimulating effect was reproduced by using the conditioned medium (CM) of the active cells but not with CM of the other cell types. A slight stimulation was also obtained when tumoral MCF7 cells and fibroblasts shared the same medium but were physically separated, suggesting that close contact was required for optimal stimulation of collagen synthesis. The collagen synthesis stimulating activity was not related to a modification of fibroblast proliferation rate. The production of collagen types I, III, and VI and fibronectin were increased in cocultures of fibroblasts with MCF7 cells. The increased synthesis of collagen types I and III and fibronectin was paralleled by similar changes in the steady-state level of their mRNAs. On the contrary, the increased production of collagen type VI appeared regulated at a post-transcriptional level.

Adenocarcinoma↗

The stimulation of fibroblasts' collagen synthesis by neoplastic cells is modulated by the extracellular matrix.

Human fibroblasts cocultured with neoplastic MCF7 cells produce increased amounts of collagen. A maximal stimulation requires direct cell-cell contacts between tumor cells and fibroblasts. However, this effect could be reproduced, although to a lesser extent, by medium conditioned by MCF7 cells, suggesting that it is mediated by a factor produced by MCF7 cells and secreted, at least partly, under a soluble form (Noël et al., 1992). This Collagen Stimulating Factor ("COSF") present in the culture medium displayed a molecular mass between 3,500 to 10,000 daltons, bound to heparin and appeared to be different from the growth factors described until now. The "COSF" can be released from the surface of MCF7 cells by treatment with heparin. The aim of the present work was to investigate the influence of various extracellular matrix components on the production and the release of "COSF". A 3- to 4-fold enhancement of collagen synthesis was observed in coculture on plastic and collagen type I substrates without significant modification of the non-collagen proteins. The increased collagen synthesis was paralleled by an elevation of specific collagen mRNAs level suggesting a regulation at a pretranslational level. On the opposite, in the presence of soluble or insoluble laminin, this stimulation was abolished. Similarly, coculture on "reconstituted basement membrane matrix", matrigel, did not increase collagen production. The "COSF" was found to bind to matrigel and could be released from the basement membrane matrix by treatment with heparin.

Adenocarcinoma↗

Acyclovir vs isoprinosine (immunovir) for suppression of recurrent genital herpes simplex infection.

OBJECTIVE: To compare the efficacy and safety of oral acyclovir (400 mg twice daily) with oral isoprinosine (500 mg twice daily) in the suppression of recurrent genital herpes. DESIGN: Double-blind, double-dummy, randomised, controlled, parallel group trial. SETTING: 13 centres in UK, Belgium and Germany. SUBJECTS: 127 immunocompetent patients with frequently recurring genital herpes. MAIN OUTCOME MEASURES: Proportions of patients reporting recurrences, recurrence frequency, and mean duration of lesions during breakthrough recurrences in each treatment group during a 6 month treatment period; time to first recurrence during treatment and follow-up after treatment cessation. RESULTS: During treatment, acyclovir recipients showed significant differences (p < 0.05) when compared with isoprinosine recipients in terms of a lower proportion reporting recurrences (31% vs 96%), a reduced mean number of reported recurrences per patient (0.6 vs 3.6), a shorter mean duration of breakthrough lesions (6.4 days vs 8.2 days), and a longer mean time (standard error) to first recurrence (143.7 (9.1) days vs 40.5 (5.4) days. The mean time to first recurrence after treatment cessation did not differ between the two groups. As compared with placebo recipients, isoprinosine treated patients had an increased recurrence frequency (3.6 vs 2.5) during treatment, and a shorter time to first recurrence after treatment cessation. All treatments were well tolerated without serious adverse events or toxicity. CONCLUSIONS: Acyclovir is very effective in suppressing recurrent genital herpes and is clearly superior to isoprinosine which is not clinically useful in the dosage studied.

Acyclovir↗

Evaluation of in vitro reconstituted basement membrane assay to assess the invasiveness of tumor cells.

The crossing of tumor cells through basement membranes represents a critical step in the metastatic process. We have used a reconstituted basement membrane (matrigel) coated on filter in a Boyden chamber to assess the invasive potential of tumor and normal cells. No correlation was found between chemoinvasion in vitro and the metastatic potential in vivo. Normal human fibroblasts and murine 3T3 fibroblasts penetrated filters coated with matrigel. On the other hand, the tumoral cells (MCF7, MCF7 gpt, MCF7 ras, BeWo, JAR, NUC-1 cells) were unable to cross the matrix. Our results suggest that in our conditions, this widely used model to assess tumoral invasion does not provide a universal assay to test the invasiveness of tumor cells. Penetration of the matrigel appears to be related to chemotactic or haptotactic responses depending upon cell types. Our data emphasize the variability of molecular events associated with basement membrane invasion.

3T3 Cells↗

A molecular biologic study of extracellular matrix components during the development of glomerulosclerosis in murine chronic graft-versus-host disease.

BACKGROUND: We studied the development of glomerulosclerosis in murine chronic graft-versus-host disease, a model for human systemic lupus erythematosus. EXPERIMENTAL DESIGN: The disease was induced in (C57BL10 x DBA/2)F1 hybrids by injection of DBA/2 lymphocytes leading to deposition of auto-antibodies in the glomeruli, and a lupus type of nephritis morphologically. We have determined the levels of mRNA coding for laminin (B1 and B2), a 67 kilodalton laminin binding protein, and types I and IV collagen, in control and graft-versus host disease mice at various times after disease induction. RESULTS: Laminin and collagen mRNAs were increased in whole kidneys 4 weeks after induction of the disease. At week 10, all animals displayed dramatic stimulation of alpha 1(I), alpha 1(IV), laminin B1, and B2 mRNAs. The 67 kilodalton laminin binding protein mRNA was also doubled from week 4 to 16. In isolated glomeruli, the mRNA level coding for laminin B2 was already significantly increased from week 8. This enhancement of laminin synthesis corresponds to the mesangial expansion and to the development of laminin-containing spike formations of the glomerular basement membrane at week 8. CONCLUSIONS: The expansion of the mesangial matrix in murine chronic graft-versus-host disease is caused at least in part, by an increased production of extracellular matrix components by glomerular cells. These results demonstrate that the increase of specific extracellular matrix components mRNAs precedes light microscopic changes. Quantitative evaluation of the mRNA levels coding for extracellular matrix proteins may reveal a useful method for the early detection of the development of glomerular sclerosis at the stage preceding the onset of anatomo-clinical changes.

Animals↗

The human placenta becomes haemochorial at the 13th week of pregnancy.

Histological specimens of recent implantation sites are the basis of our current concept on human embryo implantation and placental development. In the Carnegie Collection maternal red blood cells were detected early in the primitive intervillous space (10th-12th day after conception). These cells were localized to the trophoblastic lacunae and originated from distended peripheral maternal sinusoids (Kaufmann, 1981). The classical theory states that progressively more and more maternal vessels are tapped. A true maternal blood flow is established around the 29th day. Dynamic investigations of human placental development in vivo are scarce and hampered by ethical considerations and the absolute requirement to refrain from using non aggressive and potentially harmful techniques. Despite these limitations such studies provide new insights that surprisingly contradict our previously and seemingly definitely established knowledge of the early phases of placental vascularization, and lead us to conclude that there is an absence of maternal blood circulation in the intervillous placental space (IVS) during the 12 first weeks of human pregnancy.

Female↗

[Human placental implantation].

Like malignant tumor cells, cells of the trophoblast, of the blastocyst and of the hemochorial placenta are highly invasive. This invasiveness is essential for implantation and penetration of the epithelial and connective tissues of the endometrium. According to Hertig's data and the observations (henceforth classical) of the Carnegie Foundation, it is commonly admitted that trophoblastic cells penetrate rapidly the blood vessels of the maternal endometrium, open them and allow the establishment of a communication between maternal circulation and fetal tissues from the 20th day after fertilization. As suggested in the classical textbooks of Embryology, the hemochorial placentation would be established very early in human pregnancy. These observations (essentially histological) are actually contradicted by clinical observations performed by Doppler contact echography and by dynamic observations with a microvideo camera implanted in the intervillous placental chamber. Echographic observations coupled with the study of Doppler signals suggest the absence of placental maternal vascularization during the first trimester of pregnancy. It is possible to mount an optical system between the membranes and the uterine wall up to the placental tissue to observe the placental circulation. This direct observation concludes to the absence of maternal vascularization in the intervillous chamber during the first trimester of pregnancy. At the beginning of the 13th week of gestation, uterine arteries open directly into the intervillous chamber ensuring the direct perfusion of placental villi. These informations allow to suggest that the placenta becomes hemochorial at the beginning of the second trimester of pregnancy.

Female↗

A histologic study of the extracellular matrix during the development of glomerulosclerosis in murine chronic graft-versus-host disease.

The development of glomerulosclerosis was studied in murine chronic graft-versus-host disease (GvHD), which is a model for human systemic lupus erythematosus. The authors investigated the distribution patterns of six components of the extracellular matrix (ECM), i.e., laminin, fibronectin, collagen types I, III, IV, and VI during the course of the disease. All of these ECM components except collagen type I were found in the glomeruli of normal mice, where all of them were intrinsic constituents of the mesangium. Laminin, fibronectin, and collagen type IV were also found in the glomerular capillary walls. Starting 6 weeks after the induction of GvHD and continuing at week 8, the onset of an expansion of the mesangial matrix was observed. At the same time, the amounts of laminin, fibronectin, and collagen types IV and VI increased. Ten weeks after the onset of the disease, glomerulosclerosis developed. Traces of the interstitial collagen type I were found in sclerotic glomeruli. The levels of four ECM components, i.e., collagens III, IV, VI, and laminin were markedly decreased in the sclerotic glomeruli as compared with week 8. In contrast, the amount of fibronectin in the sclerotic glomeruli increased dramatically. Immunoelectron microscopic examination showed fibronectin in the sclerotic lesions, in contrast to laminin, collagen type I, and collagen type IV. It is concluded that the sclerotic lesions in murine chronic GvHD contain fibronectin. The small amounts of the ECM components laminin, as well as collagens III, IV, and VI in the sclerotic glomeruli in GvHD, might represent remnants of mesangial material and collapsed capillary walls. These components are probably replaced by increased production and/or accumulation of collagen type I and fibronectin.

Animals↗

Malignant cell attachment to endothelium of ex vivo perfused human umbilical vein. Modulation by platelets, plasma and fibronectin.

The success of blood-born metastatic spread depends upon a key event: the tumor cell arrest and attachment to the host organ vasculature. In the present study, we have investigated interactions between several normal and cancer cell lines and vascular endothelium in a model of ex vivo perfusion of human umbilical vein. In this system, hydrodynamic parameters are monitored and endothelial cells are kept in their original environment known to modulate their phenotype. Metastatic tumor cell adhesion to the perfused endothelium was found to be significantly higher than that of normal cells tested. Platelets and soluble plasma factors including fibronectin promoted tumor cell arrest and adhesion to endothelium. Altogether our results indicate that the ex vivo perfusion of human umbilical vein allows the study of the interactions between malignant tumor cells, circulating plasma or blood cells and the endothelium during blood-born metastatic spread.

Blood Platelets↗

Invasion of reconstituted basement membrane matrix is not correlated to the malignant metastatic cell phenotype.

Interactions between tumor cells and basement membranes represent a critical step in the progression of neoplasia and in the metastatic process. Reconstituted basement membrane matrix, matrigel, has been recently used with the aim of developing an in vitro assay of tumor cell invasiveness. We have extended these studies by comparing the invasiveness of a large series of normal and malignant epithelial and mesenchymal cells of human and animal origin cultured on matrigel. Normal cells (fibroblasts, glomerular mesangial cells, keratinocytes), human fibrosarcoma cells (HT1080), and reticular sarcoma cells (M5076) clearly established invasive capabilities in the matrix. However, all the other tested cell lines, malignant or virally transformed cells invasive in vivo (MCF7, T47D, SA52, SW613, MO4, A431, BeWo), as well as normal nontransformed cells (MOH22) were incapable of penetration. The morphological features of matrigel invasion by normal fibroblasts and HT1080 cells are described at the light and electron microscope levels. The extent of degradation of a radiolabeled matrigel is minimal and similar in several cell lines reported to be noninvasive or invasive in vivo. Our data suggest that matrigel does not provide a universal model to correlate the invasiveness of cells in vivo and in vitro.

Animals↗

Evidence that the interaction between circulating IgA and fibronectin is a normal process enhanced in primary IgA nephropathy.

A solid-phase ELISA was set up to measure the direct binding capacity (BC) of different, commercially available, purified human IgA preparations to plates coated with human fibronectin (FN). It was found that secretory, polymeric, and, to a much lesser extent, monomeric IgA exhibited elevated FN-BC as compared to their BC to plates coated with bovine serum albumin. This binding was specific since not observed with human IgG or IgM antibodies. In addition, we noted that this interaction was dose dependent, Ca2+ dependent, saturable, and not covalent, was inhibited by soluble FN, but not by a prior incubation of FN-coated plates with anti-human fibronectin antibodies, and appeared to involve on the dimeric FN other structures than its heparin-binding, collagen-binding, or C1q-binding domains. Similar experiments conducted with normal plasma indicated that plasma IgA, but not plasma IgG or IgM, was also capable of significant binding to FN-coated plates. In contrast, serum IgA did not significantly bind to those plates under otherwise identical experimental conditions. Thus, the coagulation process induces a strong decrease in the FN-BC of circulating IgA, which implies the necessity of using plasma rather than serum to study such interactions. The apparent molecular weight of plasma IgA interacting with FN-coated plates ranged between 450 and 900 kd, and its major binding characteristics were quite similar to those observed with purified polymeric IgA. The FN-BC of plasma IgA was then measured by the same ELISA in 30 patients with primary IgA nephropathy (IgAN) and in 23 healthy controls. The mean FN-BC of plasma IgA was significantly higher in patients than in normal controls. This enhancement was due mainly to the augmentation in the concentration of circulating "macromolecular" IgA and was significantly correlated with the plasma levels of IgA-FN complexes. However, the pathogenetic role of these findings was probably not determinant since similar observations were made in alcoholic liver cirrhosis without urinary abnormalities and since the FN-BC of plasma IgA or the plasma levels of IgA-FN complexes were not correlated with the various biological parameters of evolutivity of primary IgAN. In conclusion, these studies suggest that the ability of polymeric IgA to directly bind to FN is involved in the formation of circulating IgA-FN complexes and that this normal binding process, although enhanced in IgAN, is probably not responsible for kidney injury, at least in the patients studied.

Adolescent↗

Rat chromosome 5 (q22-23) contains elements that control cell morphology and interactions with the extracellular matrix: a study of normal fibroblast x malignant hepatoma cell hybrids.

Cell interactions with the extracellular matrix are consistently modified in neoplasia. Malignant transformation has been correlated with modifications in the synthesis and distribution of matrix components and with alterations of cell adhesive properties to these components. A particular class of genes, able to suppress the transformed phenotype in normal cells, may be involved in those phenotypic changes. By studying somatic cell hybrids between mouse hepatoma (BWTG3) cells and normal rat skin fibroblasts (RSF), Islam and co-workers were able to localize a gene or a group of genes controlling anchorage dependence and cell growth in vitro. This (or these) gene(s) was (were) assigned to the q22-23 fragment of rat chromosome 5. In the present study, we compare the morphology and the interactions with the extracellular matrix proteins (laminin, fibronectin, and collagen IV) and the synthesis of these proteins by RSF X BWTG3 hybrid cells that had either retained (BS181p10) or lost (BS181a5) the q22-23 region of rat chromosome 5. Our results suggest that the rat 5q22-23 fragment controls a part of the cell differentiation program including morphology, attachment to extracellular matrix, and synthesis of some matrix proteins, particularly alpha 1 and alpha 2 chains of collagen IV.

Animals↗

Expression of laminin by human fibroblasts, HT1080 fibrosarcoma cells and MCF-7 breast adenocarcinoma cells. Lack of regulation by the cell density and extracellular matrix.

We have cultured normal fibroblasts, fibrosarcoma HT1080 cells and breast adenocarcinoma MCF-7 cells on various substrates (plastic, collagen type I, laminin). All cell types used adhered on the three substrates with, however, a delayed attachment on laminin. On all substrates, cell grew as monolayer with the exception of MCF-7 cells that formed clusters on laminin. The epithelial MCF-7 cells as well as mesenchymal cells (fibroblasts and tumoral HT1080 cells) synthesized laminin and expressed mRNA coding for laminin B1 chain and for the 67 kD laminin binding protein. The levels of these mRNAs were not modulated by culture conditions which affect cell morphology nor by cell density.

Adenocarcinoma↗

Efficacy of sustained-release vaginal oestriol in alleviating urogenital and systemic climacteric complaints.

In a double-blind, placebo-controlled study, 109 patients suffering from local and vasomotor postmenopausal complaints were randomly assigned to treatment with either depot vaginal suppositories containing 3.5 mg oestriol (E3) or a placebo. The treatment schedule comprised one vaginal suppository twice weekly for 3 weeks initially, followed by maintenance therapy with one vaginal suppository weekly for the 6-month study period. The effectiveness of the therapy was assessed on the basis of questionnaires (Kupperman index for vasomotor complaints and an original urogenital index for local complaints) and gynaecological examinations which included assessments of vaginal cytology, vaginal pH and Döderlein bacilli. To rule out induced endometrial proliferation, endometrial biopsies were performed in 50 women before and after the study. The vaginal depot (E3) formulation showed highly significant superiority over the placebo with respect to therapeutic effect on local urogenital complaints and alleviation of vasomotor complaints, including hot flushes. Analysis of the endometrial biopsies indicated that the monotherapy used caused no endometrial stimulation. Taking into account the minimal rate of adverse effects, the 3.5 mg E3 depot formulation studied represents a useful variant in the range of preparations available for the treatment of post-menopausal complaints.

Administration, Intravaginal↗

Absence of laminin deposition in breast cancer and metastases except to the brain.

Laminin, a major glycoprotein of basement membrane has been found to play significant roles during invasion and metastases. In this study, we have examined the distribution of laminin in several human brain carcinoma metastases, human breast cancers, skin and lymph node metastases of breast cancer as well as in an in vitro and an in vivo model of invasion. A laminin accumulation was demonstrated a) at the border between human metastatic carcinoma cells and surrounding neural tissue; b) at the invasive edge between MO4 cells (a highly malignant cell line which synthesizes large amounts of laminin) and host tissues of syngenic mice; c) at the front of invasion between MO4 cells and precultured heart fragments in an in vitro model of invasion. Laminin, but not type IV collagen, promoted attachment of MO4 cells. This attachment was inhibited by preincubation of laminin matrix support with (+)-catechin, a flavonoid which also prevented invasion of the precultured heart fragment in vitro. Our data demonstrate that laminin accumulates between malignant cells and host tissue in human brain metastases and in an in vitro and an in vivo model of invasion. In these later models, accumulation of laminin is the consequence, at least in part, of its biosynthesis by MO4 cells. Since laminin promotes attachment of malignant cells in vitro, increases invasiveness and metastatic activities of murine malignant cells, it is tempting to speculate that laminin synthesized by invasive cells and accumulated at the front of invasion plays a significant role in the first step of invasion.

Adenocarcinoma↗

Influence of basement membrane molecules on directional migration of human breast cell lines in vitro.

Spheroidal cell aggregates were prepared from four tumorigenic human breast cell lines (HBL-100 and three MCF-7 variants). Cells from these aggregates were allowed to migrate towards lanes of basement membrane components coated on a glass substratum. Matrigel (reconstituted basement membrane) lanes permanently arrested the migration of one MCF-7 cell line, while migration of the others was permitted. Amongst several purified basement membrane constituents only laminin, not collagen type IV or fibronectin, was found to cause the same arrest of migration. Within the laminin molecule only the pepsin P1, not the elastase E8 fragment, efficiently arrested migration of that cell line. Although migration was inhibited by these components, time-lapse video recordings revealed that arrested cells still proliferated and actively ruffled on top of the coatings. These data suggest that, amongst several basement membrane components, laminin can function as a stop signal for cell migration. Within laminin, this activity seems to be mainly associated with the P1 fragment. We conclude that laminin is the major determinant of the barrier-function of the basement membrane, to which some cell types have become insensitive.

Basement Membrane↗