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Biomedical subjects

L M Franks

Publications and source records attributed to L M Franks.

At least 19 recordsLinked to original sources
PubMed1988

Analysis of metastatic competence of mouse bladder carcinoma cells after transfection with activated Ha-ras or N-ras oncogenes.

Transfection of the Ha-ras oncogene into a low metastatic epithelial cell line resulted in the acquirement of significantly increased metastatic capacity. This alteration in metastatic competence of a carcinoma line in a syngeneic system seemed to be a selective change and was not affected by parameters such as tumor latency period or local tumor growth. Transfection of the selection marker vectors with normal cellular DNA or with the N-ras gene did not lead to significantly increased metastatic capacity. Analysis of metastatic variants after oncogene transfection and in vivo selection showed integration of N-ras, but not of Ha-ras oncogenes. A possible role for the Ha-ras oncogene in the initial steps of metastasis will be discussed.

Animals↗
PubMed1988

Genetic aspects of tumour metastasis.

The application of techniques for the transfer of genetic material between cells when used with recombinant DNA technologies and gene cloning procedures hold exciting possibilities for the genetic analysis of the metastatic behaviour of tumour cells. So far these genetic studies have produced confusing results, but some of the problems have been defined more clearly. For a more complete understanding of the metastatic phenotype a more critical analysis of the models used to mimic the process and a greater appreciation of the deficiencies in the techniques applied to study it are necessary.

Animals↗
PubMed1986

Selective suppression of metastasis but not tumorigenicity of a mouse lung carcinoma by cell hybridization.

Somatic cell hybrids were produced by polyethylene glycol-induced cell fusion between metastatic CMT 167 (HGPRT-/OUAR) C57BL/Icrfat mouse lung carcinoma cells and 2 non-metastatic cell lines: C3H/He mouse L-M(TK-) cells of mesenchymal origin and EJ (OUAS) human bladder carcinoma cells. Fusion of 2 different CMT167 (HGPRT-) clones with L-M(TK-) cells followed by selection in HMT medium gave rise to 14 intraspecific hybrids, which were shown to express H-2 antigens specific for both the C57 and C3H mouse strains. Three interspecific hybrids arising from fusion of EJ(OUAS) and CMT167(HGPRT-/OUAR) cells were selected in HMT/ouabain medium and characterized by human isozyme analysis. All the hybrids produced large tumours after subcutaneous inoculation of 5 X 10(5) cells into adult athymic nu/nu mice. The intraspecific hybrid tumours were predominantly sarcomatous (mesenchymal) in structure but a few contained epithelial acini. Metastatic ability (as assessed by production of lung metastases) was completely suppressed in 13 of the 14 mouse/mouse hybrid cell clones. These results suggest that tumorigenicity, tumour structure and the ability to metastasize are expressed independently. The interspecific hybrids, which had not retained a full human chromosome complement, produced metastatic tumours that remained epithelial in structure.

Animals↗
PubMed1986

Tissue culture model of transitional cell carcinoma: characterization of twenty-two human urothelial cell lines.

Twenty-two continuous cell lines derived from normal and neoplastic urothelium, maintained under identical culture conditions, were characterized in terms of isozyme phenotype, tumorigenicity, and xenograft morphology following xenotransplantation to nude mice, cytological appearance, in vitro growth rate, labelling index, and colony-forming efficiency, in parallel with separate studies of in vitro drug sensitivities and monoclonal antibody reactivities. Three groups were identified: (a) distinct lines with differing isozyme patterns, a broad spectrum of growth characteristics, and xenograft morphologies similar to the histopathology of the parent tumors after periods of up to 17 yr following establishment in vitro; (b) cross-contaminated sublines (maintained separately in different laboratories for periods of up to 10 yr), with identical isozyme patterns and similar growth characteristics, but differing markedly in tumorigenicity and xenograft morphology; and (c) lines derived from normal urothelium which were nontumorigenic and had an isozyme pattern usually only encountered in untransformed cells. These data indicate that cell lines representative of human transitional cell carcinomas can be selected on the basis of xenograft morphology and isozyme patterns, and that a panel of lines derived from normal and neoplastic urothelium could provide a model system to study the biology and treatment of this disease.

Carcinoma, Transitional Cell↗
PubMed1985

Lactate dehydrogenase in human maxillary adenocarcinoma and in experimental adenocarcinoma in mice.

Total lactate dehydrogenase (LDH) activity and isoenzyme pattern were studied in tumour tissue from eight patients with maxillary adenocarcinoma, chronic inflammatory mucosa from 12 patients, normal maxillary mucosa from 12 patients, and an experimental lung adenocarcinoma and normal lung tissue from 12 mice. An increase in the total LDH activity and cathodic shift in LDH isoenzyme pattern was found in human maxillary adenocarcinoma as compared to normal and inflammatory mucosa. The inflammatory mucosa showed an increase in the total LDH activity and a normal isoenzyme pattern. The LDH alterations in the experimental lung adenocarcinoma in mice were similar to those in the human tumours but they were much more marked.

Adenocarcinoma↗
PubMed1984

The ability of normal mouse cells to reduce the malignant potential of transformed mouse bladder epithelial cells depends on their somatic origin.

Somatic cell hybrids have been made between a transformed mouse bladder carcinoma cell line and normal mouse bladder epithelium and mesenchyme. In the epithelial tumour/mesenchyme hybrids the malignant phenotype was expressed dominantly whereas in the carcinoma/normal epithelium hybrids the malignant potential was greatly reduced. In both cases the dominant in vitro and in vivo phenotype was that of the normal parental cells. All hybrid tumours were first palpable after 4-7 days, demonstrating that the tumours had not arisen as a result of in vivo selection of a sub-population of tumorigenic cells. Chromosome analysis showed that the carcinoma/normal epithelium hybrids were all in the hypertetraploid range but the large variation in the karyotypic profile of each hybrid made it impossible to implicate any specific chromosomes in the control of expression of the malignant phenotype. During normal development in bladder epithelium, terminal differentiation is associated with tetraploid formation by cell fusion. The reduction in malignancy of the carcinoma/normal epithelium hybrids may perhaps be due to the expression of genes associated with normal terminal differentiation after cell fusion and tetraploid formation. This is also supported by the more differentiated phenotype of the hybrid tumours. Of the 10 mesenchyme/epithelium hybrids analysed cytogenetically , four were in the hypertetraploid range from which little meaningful data could be obtained about specific chromosome losses. Chromosome analysis of the cells from the near-tetraploid hybrids showed only minor differences from what might have been expected from the input of the two parents; these differences appeared to be due to random chromosome loss. The maximum number of chromosomes lost from any of the hybrids was five, although one, two or three was more usual. The only consistent chromosome loss was of a single copy of chromosome 4, which in two of the hybrids represented the only chromosome change. The possibility that this loss might facilitate re-expression of the malignant phenotype is discussed.

Animals↗
PubMed1984

Heterogeneity in a spontaneous mouse lung carcinoma: selection and characterisation of stable metastatic variants.

The development and characterisation of a new epithelial model for the experimental investigation of metastasis is described. A tissue culture cell line CMT64 was established from a spontaneous alveolar lung carcinoma of a 17 month old female C57BL/ICRF at mouse (Franks et al., 1976). Subcutaneous inoculation of cells produces local tumours which give rise to a small number of lung metastases within three weeks. Four different tissue culture sublines CMT167, 170, 175 and 181 with increased metastatic ability were selected from pooled lung metastases by culture, mouse inoculation and reselection from lung metastases through four culture/inoculation cycles. These sublines are themselves heterogeneous and clones derived from them display marked differences in metastatic behaviour. Both CMT64 and its sublines have remained relatively stable in morphology and behavior since their origin, are fairly well differentiated, produce basal lamina even in metastases, and metastasise rapidly and preferentially to the lung after subcutaneous and intravenous inoculation in both syngeneic C57 and Nu/Nu mice (Franks & Layton, 1984). The expression of the metastatic potential of these cells is strongly influenced by the age and immune status of the host. The CMT64 system is a particularly useful model for experimental metastasis studies.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1984

Ultrastructural tumour differentiation and organ specificity in high and low metastatic lines from a mouse lung carcinoma.

A tissue culture cell line CMT64 was established from a spontaneous alveolar lung carcinoma of a C57BL female mouse (Franks et al., 1976). Subcutaneous inoculation of these cells produced a local tumour and a small number of lung metastases. Four sublines CMT167, 170, 175 and 181 with increased metastatic ability were selected, as described in the accompanying paper (Layton & Franks, 1984). The tissue culture cells and the tumours produced by all the lines are well differentiated and produce laminated surfactant-like bodies as well as basal lamina, even in metastases. No ultrastructural differences were found that might correlate with metastatic behaviour in vivo. Metastases, after subcutaneous inoculation and tumour colonies after intravenous inoculation of all cell lines are only found in the lung, but after inoculation of cells into the arterial system via the left ventricle of the heart, extravascular tumour colonies were found in many organs.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1983

Cell surface properties of high- and low-metastatic cell lines selected from a spontaneous mouse lung carcinoma.

The surface oligosaccharide residues, glycoproteins and sialyl components of CMT64 lung carcinoma cells and high-metastatic sublines CMT167 and CMT181 have been studied in culture. (1) The total cellular sialic acid content did not differ appreciably between the three lines. However, the accessibility of surface sialyl groups, measured by metabolic incorporation of [3H]NAcmannosamine followed by neuraminidase hydrolysis, was decreased from 42% in CMT64 to 25% hydrolyzed in CMT181. (2) The major plasma membrane glycoproteins of the lines were radiolabelled by lactoperoxidase iodination, metabolic incorporation of [3H]fucose or labelling in the terminal sialyl residues by the NaIO4-NaB[3H]4 method and the labelled glycoproteins were analyzed by two-dimensional gel electrophoresis. Each labelling technique identified a complex pattern of glycoproteins including a prominently labelled group of high-molecular-weight acidic sialoglycoproteins: GP200/4.9-5.1 (apparent molecular weight X 10(-3)/pl of iodoprotein); GP150/5.1-5.6; GP130/5.0-5.6; GP110/5.0; GP100/4.8 and GP100/5.0-5.4. (3) The neuraminidase-susceptible glycoproteins on CMT64 and CMT181 were identified in the isoelectric focusing separation of the two-dimensional gel separation by the charge difference caused by desialylation. The glycoproteins most susceptible to neuraminidase were the high-molecular-weight acidic glycoproteins which showed marked charge heterogeneity: GP150/5.1-5.6, GP130/5.0-5.6; GP100/5.0-5.4 and GP100/4.8. (4) Using these procedures we did not detect modifications between CMT181 and CMT64 and we conclude that the cultured cells of the sublines do not display marked surface glycoprotein alterations that reflect their enhanced spontaneous metastatic potential.

Animals↗
PubMed1983

Identification of exposed surface glycoproteins of four human bladder carcinoma cell lines.

Three cell surface protein-specific methods were used to radiolabel the major glycoproteins of four human bladder carcinoma cell lines: The well-differentiated lines RT112 and TR4 and more anaplastic lines T24 and EJ. Five acidic glycoproteins iodinated in all lines by the lactoperoxidase/125I method were designated CP-175/5.8-6.0 (apparent molecular weight X 10(-3)/pl of iodoprotein), GP-155/5.0-5.3, GP-145/4.9-5.2, GP-130/4.8-5.5 and GP-110/4.9-5.3. Another iodinated glycoprotein, GP-200/5.5-6.0, was prominently labelled in RT112 and RT4 but was not detected in T24 or EJ. GP-200 as well as GP-175, GP-155 and GP-145 were not detected by the galactose oxidase/NaB(3H)4 method and were poorly labelled by the neuraminidase-galactose oxidase/NaB(3H)4 and NaIO4/NaB(3H)4 labelling methods. The major sialogalactoproteins identified in the four lines by the neuraminidase-galactose oxidase/NaB(3H)4 and NaIO4/NaB(3H)4 methods were GP-130, and a duplet of GP-90 and GP-80 which were poorly iodinated by lactoperoxidase/125I. The galactose oxidase/NaB(3H)4 reaction was increased by between 4- and 10-fold and many additional glycoproteins were labelled after neuraminidase treatment, indicating that the cell surface galactose and N-acetylgalactosamine residues of glycoproteins are highly sialylated. In cell lines RT112 and RT4 there was prominent labelling of very high molecular weight sialogalactoconjugates that was not present in extracts of T24 and EJ.

Cell Line↗
PubMed1983

Identity of some human bladder cancer cell lines.

Recent reports on transfection of mouse cells with DNA from the established human urinary bladder cancer cell lines T24, J82 and EJ (MGH-U1), and the presence of an identical genetic modification in T24 and EJ cells have led us to examine the identity of these and other cultures of urothelial origin. By the criteria of HLA-A-B-C typing 7 and isozyme analysis, we conclude that EJ (MGH-U1) and some cultures of J82 are in fact T24 cells. However, five other bladder cancer cell lines, J82 (CO'T), RT4, RT112, TCCSuP and SCaBER, are clearly distinct from T24 by HLA typing (ref. 7) and/or isozyme patterns.

Acid Phosphatase↗
PubMed1983

Cellular heterogeneity in a tissue culture cell line derived from a human bladder carcinoma.

To study heterogeneity in a cell line derived from a human bladder carcinoma (EJ), 7 clones were isolated at low passage and examined for differences in culture behaviour, ability to grow in agar and tumorigenicity in nude mice. The parent EJ line had several distinct chromosome populations (both diploid and tetraploid), grew in agar and produced tumours in nude mice. Three of the clones had pseudodiploid modes and 4 had either hypo- or hypertetraploid modes. The 7 clones had 5 marker chromosomes in common but the combination of other marker chromosomes made each clone unique. No significant difference was found between the clones in the in vitro growth rate although analysis of in vitro culture behaviour showed heterogeneity in the pattern of cell movement on plastic substratum. Three clones were composed of static cells, one clone had very mobile cells; the other clones had rates of movement intermediate between the two. Differences were also found in the packing density of the cloned cells and in the cell size. All 7 clones grew in agar but heterogeneity was seen between the clones as shown by widely varying colony-forming efficiencies (0.5-13%). One clone had a high colony-forming ability in agar but failed to produce tumours in nude mice. The other clones were tumorigenic regardless of colony-forming efficiency in agar. Specific chromosome abnormalities were found to be associated with growth in agar and tumorigenicity but not with the growth pattern or the rate of movement of the cloned cells in culture.

Animals↗
PubMed1981

Chromosome pattern, growth in agar and tumorigenicity in nude mice of four human bladder carcinoma cell lines.

Four human bladder carcinoma cell lines have been characterized by G-banding, and the chromosomal patterns correlated to growth in agar and tumorigenicity in nude mice. Each cell line was shown to be chromosomally unique and although numerical and structural anomalies were present, none were common to all four cell lines. However, one or more copies of a structurally altered chromosome 8 were present in all four cell lines and may be associated with tumorigenicity in nude mice. A combination of three marker chromosomes was found in the more anaplastic cell lines, but not in the two well-differentiated tumour cell lines. Growth in agar may be associated with the presence of the three marker chromosomes but was not correlated with tumorigenicity in nude mice.

Agar↗
PubMed1981

Localization of species cross-reactive epithelium and urothelium specific antigens in the urinary tract of the rat, mouse, hamster and guinea pig.

Antiserum from a New Zealand white rabbit raised against the saline soluble fraction of calf bladder epithelium was absorbed to produce epithelial and urothelial specific stages. With indirect immunofluorescence antiepithelial antiserum reacted with all cell layers of the urothelium of a rat, mouse, hamster and guinea pig in all regions of the urinary tract, and in the epithelium of the renal pyramid and tubules. The most intense reaction in the urothelium was seen in the superficial cells of the rat and mouse but in the intermediate cells of the guinea pig. Urothelium specific antigens were demonstrated predominantly in the superficial cells of the urothelium as far as the fornix of the renal pelvis but not in the renal pyramids or tubules in all these rodents except for the guinea pig.

Animals↗