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M F Poupon

Publications and source records attributed to M F Poupon.

At least 109 records · Page 6Linked to original sources
PubMed1987

Antimetastatic effect of immunomodulators from Nocardia opaca in mice and rats activation of peritoneal macrophages by these fractions.

Nocardia delipidated cell mitogen (NDCM), a particulate fraction prepared from Nocardia opaca, injected i.p. in an oil/water emulsion to F6 rhabdomyosarcoma-bearing rats, inhibited the development of pulmonary metastases; 6 out of 10 rats were protected. Repeated i.p. administration of emulsified NDCM and of two other compounds, a Nocardia water soluble mitogen (NWSM a hydrosoluble fraction) and purified cell walls (CW, an insoluble macromolecular fraction) in Lewis lung carcinoma (LLC)-bearing mice resulted in a significant reduction of lung metastases. The efficiency of these fractions was enhanced by association with monokines. A combination regimen of NDCM, NWSM, and CW (100 micrograms/0.1 ml) and monokines (0.1 ml), injected i.p. in LLC-bearing mice, yielded a greater antimetastatic effect than either therapy alone. Peritoneal macrophages from mice which had been injected i.p. with NWSM or CW, when triggered either by TPA (tetradecanoyl phorbol acetate) or by zymosan, released large quantities of hydrogen peroxide and had a high rate of glucose consumption. These macrophages were activated as judged by their cytostatic activity against syngeneic P815 mastocytoma growth; they expressed biochemical markers which have been reported to characterize the activated state. Incubation of thioglycollate-elicited peritoneal macrophages with NWSM, and monokines for 72 h resulted in a cytotoxic activity against labeled LLC cells; addition of macrophage activating factor significantly increased the cytotoxic capacity of these macrophages. In view of this we postulate that the antimetastatic effect of soluble and insoluble N. opaca fractions and monokines might be mediated by activated peritoneal macrophages.

Adjuvants, Immunologic↗
PubMed1987

Immunogenic capacity of tum--variants isolated from a rat rhabdomyosarcoma.

An increasing number of reports highlight the fact that tumour cells are able to give rise in vitro to immunogenic variants, which are defined in vivo as being non tumorigenic, tum-. We have observed the emergence of immunogenic variants, derived from a primary nickel-induced rat rhabdomyosarcoma established in culture (RMS 9-4/0), resistant to treatment with the chloronitrosourea, chlorozotocin (CZT) (R-lines). They were separated from the whole population of cells by a cloning procedure. Furthermore, we demonstrate that the cloning procedure by itself allows the isolation of tum- variant designated as C-lines. In both cases, the tum- phenotype was observed after s.c. injection of cells into syngeneic rats with a broad range of R9 or C8 cells (10(4) to 10(7). This characteristic was inherited in a stable manner. Athymic mice developed tumours of rat rhabdomyosarcoma origin when grafted with 10(5) cells. Immunization of rats with one R variant (R9) tum- protected the rats grafted with the parental RMS 9-4/0 cells against metastatic invasion of the lungs, but not against local tumour growth, and rats grafted with a CZT-resistant tum+ cell variant S4T (in vivo-derived) against its hepatic and pulmonary metastases, while the local tumour progressed as usual. Immunization of rats with one C variant (C8) tum- cells did not protect them against either metastases or local growth of the implanted tumours. Both R and C lines cells became progressively resistant to NK- and macrophage-induced cytotoxicity. Splenic lymphocyte transfer from immune rats into nude mice, i.e., the Winn test, showed a complete degree of protection against C8 or R9 tumour growth. We conclude that two different antigenicities were revealed, one common to R9 and C8 cells in relation with their selection procedure by repeated cloning. Another antigenicity appeared in the R9 line, selected by CZT-resistance. The anti R9 cell immunization against CZT-resistant tum+ S4T could argue in favour of CZT action in the acquisition of R9 cell antigenicity. More likely, an amplification of antigens rather than induction of a new antigen could explain the protection of anti R9 immunized rats against parental tumour metastases.

Animals↗
PubMed1987

Inhibition of rat natural killer cell function by carcinogenic nickel compounds: preventive action of manganese.

The effects of carcinogenic nickel [(Ni) CAS: 7440-02-0] and Ni compounds on the natural killer (NK) cell activity of rat peripheral blood mononuclear cells (PBMCs) were studied. Rhabdomyosarcomas were locally induced by one im injection of Ni or Ni subsulfide [(Ni3S2) CAS: 12035-72-2] dust in the hind leg of WAG rats. A weakly tumorigenic dose of 5 mg Ni3S2 (tumor incidence, 2%) induced a transient decrease of PBMC NK activity against YAC-1 cells in vitro (from the 17th to the 23d wk after Ni3S2 inoculation), which could be restored by in vivo injections of partially purified rat fibroblastic interferon (IFN). Injection of 20 mg Ni (tumor incidence, 47.5%) produced a long-lasting depression of NK cell activity (from the 8th to the 23d wk). In vivo chronic IFN treatment of the Ni-injected rats neither restored NK cell activity nor affected the tumor incidence. However, NK cells of Ni-treated animals responded normally to IFN in vitro. Prospective analysis of individual NK cell responses showed that a persistent depression of basal NK cell activity was restricted to rats that subsequently developed a tumor. In these animals the time between carcinogen treatment and clinical detection of the primary tumor was positively correlated with the mean level of NK cell activity (3-4 determinations/rat). Admixture of manganese to Ni inhibited the development of tumors and also prevented the depression of NK cell activity produced by Ni alone. Noncarcinogenic Ni oxide stimulated NK cell activity. These results point out the possible involvement of NK cells in resistance to Ni-induced carcinogenesis.

Animals↗
PubMed1986

Cell surface glycosaminoglycans of rat rhabdomyosarcoma lines with different metastatic potentials and of non-malignant rat myoblasts.

Glycosaminoglycans of cultured nickel-induced rat rhabdomyosarcoma cell lines with different metastatic potentials and of non-malignant myoblasts, grown in the presence or in the absence of hydrocortisone, were studied comparatively. The newly formed [3H]glucosamine-labelled cell surface proteoglycans and glycosaminoglycans were separated by ion exchange chromatography and partially characterized. The overall incorporation of the label in the glycosaminoglycan fractions and the average molecular weight of the heparan and of the chondroitin sulfate proteoglycans was lower in the malignant cells than in the non-malignant L6 myoblasts. The strongly metastatic 9-4/0 parental line and the 6 subline were relatively richer in chondroitin sulfate and poorer in dermatan sulfate labels than the very weakly metastatic 8 subline and the L6 myoblasts. Hyaluronic acid and heparan sulfate labels were inversely related to the metastatic capacity of the cell lines studied. Hydrocortisone treatment induced an increase in the cell surface chondroitin and dermatan sulfate labels in the case of the strongly metastatic lines, and a decrease of the same parameters in the case of the weakly metastatic 8 line.

Animals↗
PubMed1986

Transglutaminase activity and putrescine-binding capacity in cloned cell lines with different metastatic potential.

An inverse correlation was found between cellular transglutaminase activity and metastatic potential of four cloned cell lines derived from a primary nickel-induced rat rhabdomyosarcoma. Cellular transglutaminase activity as assessed with endogenous cellular protein or exogenous methylated casein was greatest in the clone F9-4/8 which is the least metastasizing. When the putrescine-binding capacity of one cellular derived protein - fibronectin - was examined with exogenous transglutaminase, it was found that the fibronectin derived from the clone F9-4/8 showed the lowest binding capacity compared with those from the other clones. However, when the overall binding capacity of cellular proteins from each cell line was examined no differences could be detected. The results are discussed in the light of the well-known role of fibronectin in cellular adhesion.

Animals↗
PubMed1986

Influence of the uremic state on the development of malignancy. An experimental study in the rat.

The effect of chronic uremia on the development of subcutaneously injected malignant tumoral cells was evaluated in 213 male Wistar AG rats made chronically uremic by simultaneous right nephrectomy and partial ligation of the left renal artery. The tumoral cells injected were stemming from a parental rhabdomyosarcoma (9-4/0) induced by intramuscular injection of 20 mg of colloidal nickel suspended in oil to a male Wistar rat. 54 sham-operated rats and 43 nonoperated animals served as control-groups. Renal function and tumoral growth were checked weekly up to the 60th postoperative day, at which time the surviving rats were sacrificed and submitted to autopsy. At day 15 after cell grafting, a tumoral lump could be felt by finger touch in 68% of the uremic rats, but in only 11% of the sham-operated and 14% of the nonoperated controls (p less than 0.0001). Throughout the study, the tumoral lumps which developed in the uremic animals were of significantly larger size than in the nonuremic controls. Pulmonary tumoral metastases were evidenced at autopsy in 95% of the uremic rats, but in only 50% of the sham-operated and in 54% of the nonoperated controls (p less than 0.005). These results indicate an apparently accelerating and amplifying effect of uremia on the development of a malignant tumor in the rat, for which a decrease in cell-mediated immunity associated with the uremic state still remains a questionable hypothesis.

Animals↗
PubMed1986

Chromosome analysis of rat tumor cell lines associated with metastatic potential and drug resistance.

Seven rat rhabdomyosarcoma cell lines, 9-4/0, F6, F8, F13, F21, R3 and R9, were cytogenetically investigated. They differed in their metastatic, tumorigenic and growth potential, and in resistance to chlorozotocin (CZT = 2,3-[2-chloroethyl]-3-nitrosoureido-beta-D-glucopyranose). No strict correlation between phenotypic features and chromosomal aberrations existed; however, rearrangements specific for each line were found. Twenty-one chromosome markers, present in a minimum of 20% of cells of a line, were observed. Chromosomes 3, 7, 10, 11 and 13, were those most often involved in marker formation. Two CZT-resistant lines, R3 and R9, showed no common aberration, but R9 which was most resistant, was shown to have a homogeneously staining region, which is usually thought to be the site of gene amplification.

Animals↗
PubMed1986

Enhancement of pulmonary metastases induced by decreased lung natural killer cell activity.

Administration of repeated high doses of 7.5 mg chlorozotocin [(CZT) CAS: 54749-90-5]/kg to syngeneic WAG rats bearing the rhabdomyosarcoma 9-4/0 enhanced the incidence of spontaneous metastasis compared to its incidence in untreated rats. This enhancement was observed concomitantly with an increase in the survival of 9-4/0 rhabdomyosarcoma and P 77 fibrohistiocytoma tumor cells, labeled with [125I]5-iodo-2'-deoxyuridine or 51Cr and injected iv. Within the first 24 hours after P 77 cell injection, the lungs retained 10% of the cells while the lungs of controls or of rats given one CZT injection only retained 0.06%. The natural killer (NK) cell cytotoxicity of cells flushed out from lung capillaries [lung intracapillary cells (LIC)] was studied concomitantly in a 4-hour 51Cr release assa against YAC-1 and P 77 target cells. A large reduction was again observed in NK cytotoxicity but only after repeated injections of 7.5 mg CZT/kg. Lung defenses were gradually restored after treatment stopped. Administration of polyinosinic-polycytidylic acid with CZT restored the NK cell cytotoxicity of LIC and inhibited lung metastases amplification. The close relationship between metastasis and NK activity indicates the need for caution as regards the effects of chemotherapy on NK activity.

Animals↗
PubMed1986

Solubilization and degradation of extracellular matrix by various metastatic cell lines derived from a rat rhabdomyosarcoma.

Examination by use of WAG syngeneic female rats was made on 4 rat rhabdomyosarcoma sublines expressing different metastatic potentials for their abilities to degrade proteoglycans and glycoproteins of the extracellular matrix (ECM), deposited by corneal endothelial cells and metabolically labeled with [3H]glycosamine and [35S]sulfate. Of the label incorporated in ECM, 10-20% was released in the culture medium in 3 days by the cell lines studied. The proteoglycans, glycosaminoglycans, and glycoproteins released by the cells from ECM were separated and partially characterized. Most of the ECM glycoproteins were recovered in the region of 200,000 (200K) on gel chromatography. Glycopeptides of 10K-20K apparent molecular weight were minor components. The glycosaminoglycan chains of the proteoheparan sulfate were partially hydrolyzed to 20K fragments. Tumor cells increased also the solubilization of the nondegraded matrix macromolecules. About 5-8% of the radioactivity of the ECM remained associated with the tumor cells detached from the ECM. ECM degrading activity of the sublines did not correlate with their ability to colonize the lungs after iv injection but did correlate with their ability to metastasize to the lungs from the primary subcutaneous site.

Animals↗
PubMed1986

Fibroblast-dependent tumorigenicity of cells in nude mice: implication for implantation of metastases.

The inadequate nature of the microenvironment is one of several factors considered in the failure of tumor engraftment in athymic mice; in the present work, we have tried to more adequately reconstitute it by injecting tumor cells together with fibroblasts. We have demonstrated that the s.c. co-inoculation of fibroblasts with different kinds of tumor cells of animal origin [rat rhabdomyosarcoma (RMS) 9-4/0, rat hepato-carcinoma FAO] or human origin (colonic adenocarcinoma HT29, Ewing's sarcoma pleural metastasis EW-S1) is necessary for tumor take and growth when the number of tumor cells alone is below the tumorigenic dose. We have shown that the s.c. coinoculation of 10(6) fibroblasts and 10(2) RMS 9-4/0 tumor cells induced a tumor take in all the recipient mice, while 10(2) tumor cells alone never gave any tumor. With a tumorigenic number of RMS 9-4/0 tumor cells (10(4), addition of 10(6) fibroblasts decreased the delay between cell injection and tumor appearance, thereby increasing tumor take and growth rate. These results were observed not only in nude animals (mice and rats) used as recipient animals but also in normal WAG rats receiving the syngeneic RMS 9-4/0 tumor cells, and they were independent of the nature or origin of the different fibroblasts cells. This helper effect has also been observed in the normal WAG rats. I.v. injection of tumor cells from a poorly metastatic 9-4/8 subline, derived from the RMS 9-4/0 line and mixed with 10(6) fibroblasts, gave a high number of lung colonies. Addition of 10(6) irradiated 9-4/8 tumor cells instead of fibroblasts did not increase the lung colonizing potential. Fibroblast-conditioned medium mixed with tumor cells instead of fibroblasts also enhanced tumor take and size but to a lesser extent than did the fibroblasts themselves. Only endothelial cells cultured from porcine aorta had a similar helper effect among the cells tested. It is argued in the discussion that the proliferating state of cultivated fibroblasts is a determinant factor conferring upon them the ability to promote tumor cell growth, while fibroblasts very numerous at the implantation site but quiescent might not be efficient in cooperation. Changes in fibroblast morphology and physiology may be necessary in order for tumor cells to express their tumorigenicity.

Animals↗
PubMed1986

Differential adhesiveness of rhabdomyosarcoma-derived cloned metastatic cell lines to vascular endothelial monolayers.

A series of 11 cloned cell lines derived from a primary, nickel-induced rat rhabdomyosarcoma was evaluated for their metastatic capacity (number of lung colonies following i.v. injection) and attachment kinetics to confluent pig endothelial cell monolayers grown in vitro. The morphology of the adhering cells was also studied by optical and scanning electron microscopy. Cells from all lines tested began to attach to the endothelial monolayers within 15 min of incubation at 37 degrees C, with 64% to 93% of the cells adhering after 2 h. Attachment rates at 30 min ranged from 29 to 48% for four lines classed as "weakly adhesive" (attachment, less than 50%) and from 53 to 78% for seven lines classed as "highly adhesive" (attachment, greater than 50%). Four clones of five displaying low lung-colonizing capacities also showed low attachment rates to endothelial monolayers in vitro. All of six highly colonizing lines studied had high attachment rates. A degree of positive correlation was observed between the amount of cell surface fibronectin as evaluated by immunofluorescence and the early phase attachment rates (and lung-colonizing capabilities) of the different cloned cell lines. Early (15 min) attachment of tumor cells to isolated extracellular matrix preparations proceeded at higher rates than to endothelial monolayers, and previously detected differences between high- and low-colonizing clones were less evident with these matrix substrates. Our results suggest possible interrelationships between specific cell adhesion properties and the metastatic potential of blood-borne tumor cells.

Animals↗
PubMed1985

Enhanced cloning efficiency of murine rhabdomyosarcoma cells after chlorozotocin treatment: relationship with enhanced lung metastasis.

The effect of chlorozotocin [(CZT) CAS: 54749-90-5; 2-(3-(2-chloroethyl)-3-nitrosoureido)-D-gluco-pyranose] was studied on a series of tumor cells, cultured or extracted fresh primary or transplanted tumors, by means of clonogenic assay. The ability of most rat rhabdomyosarcoma cells to form colonies in soft agar was enhanced when exposed to the water-soluble nitrosourea chloride CZT. The tumor cells tested were derived from a) several primary tumors induced in WAG rats by colloidal nickel, then cultured and exposed to CZT early during in vitro passage; b) the 9-4 tumor, also Ni-induced but maintained in long-term culture; and c) the Ni-induced 9-4/0 tumor, maintained by transplantation in syngeneic rats. No inhibition of colony formation was observed in any of the cell lines even at high concentrations of CZT. Adriamycin, chosen as a control treatment, strongly inhibited the cloning efficiency (CE) of the tumor cells. In vivo, the weekly injection of 10 mg CZT/kg body weight into syngeneic rats bearing transplanted tumors led to an enhancement of lung metastasis formation. The CZT enhancement of CE of tumor cells and its relationship to increased in vivo tumor metastasis is discussed.

Animals↗
PubMed1985

Increased level of amplification of the c-myc oncogene in tumors induced in nude mice by a human breast carcinoma cell line.

Cell line SW 613-S, derived from a human breast carcinoma, contained double minute chromosomes (DMs) but lost them progressively upon in vitro cultivation. These cells were tumorigenic in nude mice. Cell lines were derived from the tumors and were found to have a high DM content. In three such cell lines, DMs were stably maintained upon in vitro cultivation, whereas in another they were progressively lost. We found that the c-myc oncogene is amplified 5- to 10-fold in SW 613-S and 20- to 90-fold in the different cell lines derived from the tumors. At least part of the additional c-myc copies were found associated with a purified DM fraction. In cell lines which lost the DMs during in vitro passages, the level of amplification was maintained. In situ hybridization experiments indicated that this loss was compensated by the acquisition of copies of the c-myc gene integrated into a chromosome. No major rearrangement of the amplified c-myc gene was detected. The amount of c-myc messenger RNAs is roughly proportional to the level of amplification. Our results indicate that growth of SW 613-S cells as tumors in nude mice selected cells with an increased level of amplification and expression of the c-myc oncogene.

Animals↗
PubMed1984

Suppressor T cells in BCG-treated mice interfere with an in vivo specific antitumoral immune response.

The interference by BCG in the induction and expression of a specific antitumoral immune reaction was studied in B6 mice, using the in vivo Winn assay and also active immunization. T cells immunized against MCA-induced fibrosarcoma (MC B6-1) transferred together with the tumour cells protected the syngeneic host against tumour take. Pretreatment of normal B6 mice with moderate or high doses of BCG prevented the development of a protective immune response after immunization. Moreover, a single dose of 1 mg, or 2 doses of 0.01 mg BCG, completely eliminated an established antitumour immunity. Suppressor cells are involved in the BCG-induced inhibitory effect; they interfered (1) with the expression of the antitumour response, since their addition to immune T cells in the Winn test resulted in decreased protection and (2) with the induction of the antitumour response, since injection of spleen cells from BCG-treated mice (BCG SpC) into normal mice before immunization inhibited the development of immunity. Treatment of BCG SpC with anti Thy 1.2 and anti Lyt 1.2 antibodies plus complement before injection into normal mice significantly decreased the suppressive activity, showing that the suppressor cells induced by BCG are T cells expressing the Lyt 1+ phenotype. The partial increase in protection obtained after IL-2 administration to BCG-treated mice suggests that the suppressive action of BCG SpC on the IL-2 producing capacity of helper T cells is only one of a number of possible mechanisms of T-cell-mediated suppression.

Animals↗
PubMed1984

Role of lysosomes in gallium concentration by mammalian tissues.

Two microanalytical methods, electron probe X ray analysis (E P M A) and ion mass analysis (I A M) were used to study gallium incorporation in normal tissues (kidney, liver, mammary gland, bone marrow, bone tissue) and in experimental tumors. The very high sensitivity of I M A makes possible the detection of very low concentration of gallium (1 ppm) with a spatial resolution of 0.5 micron, on the other hand, E P M A of lower sensitivity (100 ppm) makes possible the relation between the gallium concentration and the ultrastructure of the cell. It was shown that gallium is concentrated in the lysosomes of both types of tissues, where it is precipitated in an insoluble form. In addition, gallium is systematically combined with phosphorus in these precipitates. These observations suggest an active intralysosomal concentrating mechanism related to the presence of local phosphatase activity.

Animals↗
PubMed1984

Electron microprobe in vitro study of interaction of carcinogenic nickel compounds with tumour cells.

The effect of various nickel salts on cultured rhabdomyosarcoma cells was studied. Certain of these compounds, e.g., nickel subsulfide (Ni3S2) and nickel itself, induce tumours in muscle, while others have no effect, e.g., nickel monoxide (NiO). It has been suggested that the carcinogenicity of nickel is related to its penetrating power (phagocytosis) in transformed cells. We have used electron microscopy and microanalysis to study the ultrastructure and intracellular localization of nickel in ultra-thin sections. Nickel subsulfide and nickel monoxide penetrate into cells and are concentrated in vacuoles, exhibiting a particular affinity for membrane structures. They subsequently appear to be eliminated in the extracellular medium. Colloidal nickel and iron carbonyl, on the other hand, do not penetrate cells. Various tumoral and normal cell lines were compared for their ability to phagocytose nickel subsulfide and it was found that the compound penetrated only macrophages and impregnated the membranes of polynuclear cells. These results suggest that the phagocytosis of nickel compounds is not directly related to the eventual induction of a tumour. No nuclear localization could be detected, but we did demonstrate a mechanism for the concentration and elimination of these compounds in certain tumour cells.

Animals↗