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M F Poupon

Publications and source records attributed to M F Poupon.

At least 145 records · Page 8Linked to original sources
PubMed1976

Evidence for splenic suppressor cells in C3H/He, T-cell-deprived C3H/He, and nude mice bearing a 3-methylcholanthrene-induced fibrosarcoma.

Suppressor cells were demonstrated in the spleens of C3H/He mice carrying 3-methylcholantrene-induced fibrosarcomas. These cells inhibited the in vitro reactivity of normal lymphocytes to T- and B-cell mitogens. They disappeared within a few days after the tumor was surgically removed. Pretreatment of spleen cells (ScC) from tumor-bearing (TB) mice with either iron and a nagnet, antiserum against Thy 1.2 antigen plus complement, or antiserum against immunoglobulin plus complement demonstrated that the suppressor cells were adherent, non-T-cells bearing immunoglobulin at their surfaces. The suppressive effect could still be demonstrated by addition of SpC from TB mice 24 or 48 hours after phytohemagglutinin stimulation of normal SpC, SpC from TB C3H/He mice inhibited mitogen-induced stimulation of both C3H/He and DBA/2 lymphocytes. In T-cell-deprived TB C3H/He mice, suppressor cells were also observed and had the same characteristics as those in non-T-cell-deprived mice. In nude mice, however, although suppressor cells were active, they were not adherent and did not bear immunoglobulin at their surfaces. The existence of these suppressor cells may be one reason why the immune system of TB animals is unable to reject the tumor.

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PubMedDate not supplied

Effects of glycosaminoglycans and extracellular matrix components on metastatic rat rhabdomyosarcoma tumor and myoblast cell proliferation.

Experiments were performed to determine the relative effects of glycosaminoglycans and extracellular matrix components alone or in association with various substrates, including extracellular matrix, on the proliferation of rat rhabdomyosarcoma (RMS) cell lines of different metastatic potential and nontumorigenic rat myoblast L6 cells. The assays used various substrates: tissue culture plastic, type I and IV collagen, fibronectin, laminin and extracellular matrix deposited by corneal endothelial cells. In control experiments, tumor cells grew faster on fibronectin and extracellular matrix than on the other substrates, and their proliferation rate was decreased slightly by laminin. Collagens were growth-inhibitory only for the highly metastatic line. The proliferation rate of L6 myoblasts was not greatly affected by the different substrates. The addition of exogenous glycosaminoglycans to the culture medium modified cell proliferation on the various substrates. Heparin inhibited the growth of all the cell lines tested, independent of the substrate. When cultured on laminin substrate the proliferation rates of the cell lines were depressed by addition of heparan sulfate to the medium, and this effect was more pronounced in the metastatic RMS lines. Chondroitin sulfate and dermatan sulfate enhanced the growth rates of the tumorigenic cells when cultured on collagen type I surfaces. Hydrocortisone, which induces myogenic differentiation, decreased the cell proliferation rates of all the cell lines tested and intensified the inhibitory effects of heparin when added simultaneously to the culture medium. The results showed that glycosaminoglycans and other matrix components can affect the proliferation rates of rhabdomyosarcoma cell lines.

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PubMedDate not supplied

Hyaluronate-binding proteins in weakly and highly metastatic variants of rat rhabdomyosarcoma cells.

Weakly (RMS8) and highly (RMS0) metastatic rat rhabdomyosarcoma cells were assayed for their interaction with hyaluronate. The cells in subconfluent cultures were incubated with 35S methionine, the cells were fractionated and the labelled proteins were separated by affinity chromatography on hyaluronate-Sepharose and by HPLC. The RMS8 cells expressed about twice the amount of labelled hyaluronate-binding proteins seen in the RMS0 cells. The molecular sizes of the main hyaluronate-binding proteins were similar in both cell types. Unlike the RMS0 cells, the RMS8 cells took up exogenous, radioactively labelled hyaluronate at 4 degrees C in a saturable and specific way with high affinity. Cells were also incubated with 3H glucosamine. The isolation of the glycosaminoglycans from these cultures by ion-exchange chromatography indicated that the RMS8 cells retained more endogenous 3H hyaluronate in their pericellular domain than did the RMS0 cells. The attachment of trypsinized cells could be inhibited with exogenous hyaluronate, indicating that the proteins with affinity for hyaluronate may act as hyaluronate-binding sites on these cells.

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Association of SIBA treatment and a Met-depleted diet inhibits in vitro growth and in vivo metastatic spread of experimental tumor cell lines.

We have used 5'-deoxy-5'-S isobutyl-thioadenosine (SIBA), an analog of S-adenosylhomocysteine, alone or in association with a methionine-depleted diet in order to obtain an antitumoral effect in two different tumor models: a transplantable rat rhabdomyosarcoma (RMS-J1) induced by i.m. injection of nickel and the well-known Lewis lung carcinoma (3LL) of C57BL/6 mice. Since SIBA has been reported to inhibit the methyl group transfer from methionine to S-adenosylhomocysteine, among other activities, its association with a reduction of methyl donors, achieved by methionine depletion of the diet (in vivo) or the culture medium (in vitro), should logically lead to an additive effect. In vitro, 3LL and RMS-J1 were sensitive to the cytotoxic effect of SIBA and were methionine-dependent for their proliferation. Fibroblast proliferation was not affected by these two treatments alone or in association. In vivo, either SIBA treatment or a low methionine diet led to a significant decrease in the metastatic character of these two tumors; however, local tumor growth was not significantly affected. The median number of 3LL metastases counted in the lungs was reduced from 100 to 18 by SIBA treatment, and to 27 by the low methionine diet. No additive effect could be detected when the treatments were given simultaneously. RMS-J1-bearing rats treated with SIBA and fed a low Met diet underwent primary tumor excision. The median numbers of lung metastatic nodules were 27, 26, 14 and 8 for the control, SIBA-treated rats, methionine-deprived rats and rats receiving the combined therapy. Expressed as percentages 20 per cent were cured, 23 per cent showed a low number of lung metastases (P less than 10), whereas all the rats in the control group developed more than 10 pulmonary nodules. No cytotoxic effect could be observed on the treated rats. The role of SIBA and methionine depletion, as agents interfering with transmethylation processes, in regard to the control of tumor development, namely metastatic invasiveness, is discussed.

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Modulation of proteoglycan metabolism by hydrocortisone and by growth factors in rhabdomyosarcoma cell lines of different metastatic potentials.

Glycosaminoglycans of cultured nickel-induced rat rhabdomyosarcoma cell lines with different metastatic potentials, grown in the presence or in the absence of hydrocortisone and of growth factor (EDF and EDGF) were investigated comparatively. The newly formed [35S]sulphate and [3H]glucosamine-labelled glycosaminoglycans were analysed in the extra-, peri- and intra-cellular compartments of the following cell lines: the strongly metastatic and colonizing 9-4/0 parental line, the very weakly metastatic and weakly colonizing subline 8 and the very weakly metastatic but colonizing subline 13a2. The cell surface of the weakly metastatic 8 and 13a2 lines was richer at least 5 and 2 times respectively in sulphated glycosaminoglycan label than the surface of the strongly metastatic 9-4/0 parental line. Hydrocortisone provoked an approximately four-fold increase in the label of the sulphated cell surface glycosaminoglycans of the 9-4/0 line. The pattern of the labelled cell surface glycosaminoglycans of these cells become similar to that of cells from the very weakly invading subline 8. Hydrocortisone induced only minor changes in the distribution of the glycosaminoglycans in the 8 and 13a2 lines, and at the same time, their proliferation rate and differentiation state was only slightly affected by this drug. Conversely to hydrocortisone, EGF increases the proliferation of the 9-4/0 line and also increases the label in sulphated cell surface glycosaminoglycans. This increase is about 50 per cent of that obtained by hydrocortisone. Thus, the accumulation of the glycosaminoglycan label on the cell surface is not directly related to the cell growth in the case of these cells. The results suggest that sulphated cell surface glycosaminoglycans, especially chondroitin sulphate, are involved in the inhibition of metastasis formation of the rhabdomyosarcoma cell lines studied.

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PubMedDate not supplied

Laminin-mediated adhesion in metastatic rat rhabdomyosarcoma cell lines involves prominent interactions with the laminin E8 fragment.

In vitro attachment assays were carried out to assess adhesion between two basement membrane proteins, type IV collagen and laminin, and rat rhabdomyosarcoma (RMS) cell lines with different metastatic potentials. Whereas cells did not adhere to type IV collagen, adhesion to laminin appeared to be very sensitive as maximal adhesion was achieved in dose-response assays with only nanograms of laminin. Adhesion was mediated by interactions between coated laminin and cell surface components, probably receptors, but not endogenous laminin. Laminin-mediated adhesion of RMS cell lines was compared with that of the MCF-7 (human mammary carcinoma) and the L6 (rat myoblast) cell lines. In dose-response assays, RMS cell lines required 10 times less laminin to reach half-maximal attachment rates than MCF-7 and L6 cell lines. Two laminin fragments, P1 and E8, which are structurally and immunologically distinct as shown by alpha-helix content, SDS-PAGE and monoclonal antibody mapping, supported adhesion by RMS cells and L6 myoblasts, but MCF-7 adhered only to P1. This fragment was 10 times less active than laminin in RMS cell lines. Attachment in dose-response assays and adhesion inhibition studies by antibodies revealed that E8 accounted for the activity of laminin in RMS cell adhesion. Adhesion in the RMS cell lines was dominated by interaction with E8 regardless of metastatic potential.

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PubMedDate not supplied

Response to 5-fluorouracil of orthotopically xenografted human colon cancers with a microsatellite instability: influence of P53 status.

Response to 5-FU of 5 different human colon cancers (hCC) with a DNA microsatellite instability (MSI), xenografted into nude mice, was analysed according to their p53 status. Two hCC (TC82 and TC71) had a mutated p53 (mutp53), while two others (TC33 and LoVo) had a wild type p53 (wtp53); the fifth tumour (X17LoVo) originated from the stable transfection of LoVo cells with a dominant mutp53 (273his) vector. All tumours were implanted onto the caecum of nude mice to induce orthotopic growth of hCC. 5-FU was administered at 40 mg/kg per day for 5 consecutive days. A significant growth inhibition of TC82 and TC71 tumours (of 68 and 60%, p < 0.05 and < 0.01 respectively) was observed, whereas 5-FU had no effect on TC33 and LoVo. Moreover, the mutp53 transfected tumour, X17LoVo, displayed significant sensitivity to 5-FU (p < 0.05). This suggests that distinct genetic alterations influence differently the response of hCC to this antimetabolite.

Adenocarcinoma↗
PubMedDate not supplied

[Recent data on the immunology of tumors. Mechanisms of escape of immunological control. Role of suppressor cells].

Cells in spleens from tumor bearing animals were found to inhibit in vitro reactivity of lymphocytes to a variety of stimulants. These suppressor cells inhibited the stimulation of normal lymphocytes by mitogens : P.H.A.-Con A-L.P.S. They were adherent cells, bore immunoglobulins at their surface and did not bear the 0 marker. They were also demonstrated in T deprived tumor bearing animals. They might be B cells, or, more probably, macrophages. Other activities that are inhibited by the suppressor cells are: -reactivity to allogenic cells in the mixed lymphocyte culture, -in vitro generation of secondary anti tumor cytotoxic effector cells, -macrophage migration inhibition in the presence of immune lymphocytes and tumor extracts, -reactivity against syngeneic tumor cells or tumor extracts. Suppressor cells may play a role in the general immunodepression of tumor bearing hosts, and in the inability of tumor bearing hosts to reject the tumor. However, the biological role of these non T suppressor cells is not clear, as they also inhibit tumor cell growth, and in vivo experiments favour suppressor cells of thymic origin.

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PubMedDate not supplied

Topoisomerase I-DNA covalent complexes in human colorectal cancer xenografts with different p53 and microsatellite instability status: relation with their sensitivity to CTP-11.

The topoisomerase I poison CPT-11 has proved efficient for the treatment of untreated metastatic colorectal cancers (CRC) and those refractory to fluoropyrimidines. However, the interpatient variability is important. A previous in vitro study suggested that measurements of the level of topoisomerase I-DNA intermediates trapped by camptothecin may be useful to estimate the chemosensitivity of colon carcinoma cell lines. To verify this hypothesis, we developed an immuno-assay to detect covalent topoisomerase I-DNA complexes in a series of human colorectal cancers xenografted in nude mice. Six human CRCs were selected for their distinctive p53 and microsatellite instability (MSI) status. Tumour lysates, prepared from mice untreated or treated with CPT-11, were fractionated onto CsCl gradients to separate free and DNA-bound topoisomerase I by centrifugation. Interestingly, significant levels of DNA-topoisomerase I complexes were detected in the tumours most responsive to the treatment with CPT-11, irrespective of their MSI and p53 phenotypes. Our in vivo study fully agrees with the predictions from the in vitro data indicating that evaluation of topoisomerase I-DNA complexes would be useful to predict the response of CRC to a treatment with CPT-11.

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