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K Scotlandi

Publications and source records attributed to K Scotlandi.

68 records · Page 4Linked to original sources
PubMed1989

Modulation by IFN-gamma of the metastatic ability of murine, human, and H-2-transfected tumor cells.

Interferon-gamma (IFN-gamma) can enhance the experimental metastatic ability of B16 melanoma. The in vitro treatment with IFN-gamma of four clones derived from the murine mammary adenocarcinoma TS/A increased the number of lung colonies observed after intravenous injection in syngeneic mice. The spontaneous metastatic ability of these clones was not altered by the IFN-gamma pretreatment nor by daily intratumor injection of low-dose IFN-gamma. The experimental metastatic ability in nude mice of the human rhabdomyosarcoma cell line RD was decreased by in vitro pretreatment with IFN-gamma. To study the role played by major histocompatibility complex gene products in the IFN-gamma-mediated enhancement of B16 experimental metastasis, a mutant B16 clone, B78H1, was transfected with the H-2Kb gene. B78H1 cells are not capable of expressing H-2b even after treatment with IFN-gamma; IFN-gamma readily induced high levels of H-2Kb in a set of transfected clones, but did not enhance their experimental metastatic ability.

Animals↗
PubMed1989

Myogenic differentiation of human rhabdomyosarcoma cells induced in vitro by antineoplastic drugs.

The effect of various antineoplastic drugs (1-beta-D-arabinofuranosylcytosine, 5-azacytidine, cisplatin, dactinomycin, epirubicin, vincristine, and the activated metabolite of cyclophosphamide, mafosfamide) on cell differentiation in vitro was investigated using a human alveolar rhabdomyosarcoma cell clone, RMZ-RC2. These cells are able to differentiate spontaneously from small mononuclear proliferating elements to terminal, extremely elongated multinuclear structures resembling myotubes; morphological differentiation is accompanied by the expression of myosins, in particular the embryonic isoform, which was used in this study as a specific marker of myogenic differentiation. The proportion of differentiated myosin-positive cells, which was around 10-15% in control cultures 10-15 days after seeding, was increased by some drug treatments up to 30-40%; the proportion of multinuclear elements was also increased. 1-beta-D-arabinofuranosylcytosine and 5-azacytidine were the most effective drugs, while dactinomycin had no effect; other molecules ranked in between. Since significant increments were usually observed after treatment with drug doses inhibiting cell growth, the kinetic behavior of the absolute number of myosin-positive cells or nuclei was analyzed to assess whether some effects could be due to a negative selection of proliferating, undifferentiated cells. This appeared to be the case for vincristine and epirubicin, while 1-beta-D-arabinofuranosylcytosine, 5-azacytidine, and, to a lesser degree, mafosfamide and cisplatin actually seemed to increase differentiation ability.

Antineoplastic Agents↗
PubMed1989

In vivo and in vitro production of haemopoietic colony-stimulating activity by murine cell lines of different origin: a frequent finding.

The production of colony-stimulating factor (CSF) by murine transformed cells was investigated in 10 cell lines derived from spontaneous or chemically induced tumours and from cells transformed by SV40 or Moloney-MSV; histologic types included carcinomas, sarcomas and melanoma. Nine of 10 supernatants contained CSF activity as judged by in vitro proliferation and differentiation of normal murine monocytic and granulocytic progenitors in agar cultures. Tumours induced with CSF-producing cells caused alterations of haemopoiesis which can include leukocytosis, granulocytosis and splenomegaly. Haemopoietic alterations were also evident in the absence of a local tumour in mice bearing large experimental lung metastases. Production of CSF seems to be a frequent finding among murine cell lines, and its biological and immunological consequences on host-tumour relationships should be taken into account.

Animals↗
PubMed1989

Tumorigenic and metastatic ability of SV40-transformed BALB/c cell lines and MHC antigen expression.

Tumorigenic and metastatic potential were studied in relation to class I MHC expression in four different SV40-transformed BALB/c cell lines. All the lines studied, tumorigenic or not, expressed both H-2Kd and Dd, so MHC antigens did not seem to be involved in the control of SV40-transformed cells' growth in vivo. Lung metastases were observed in all tumour-bearing mice. Cells cultured after in vivo passage, obtained either from tumour tissue or from individual lung metastases, still expressed similar levels of H-2d antigens, thus suggesting that tumour growth and metastasis do not occur through the selection of variants with altered MHC expression.

Animals↗
PubMed1989

Human rhabdomyosarcoma cells in nude mice as a model for metastasis and differentiation.

We investigated the ability of alveolar (RMZ-RC2) and of embryonal (RD) human rhabdomyosarcoma cell lines to grow and metastasize in nude mice. Both cell lines produced local tumors, but failed to give rise to spontaneous metastases. When RD cells were injected intravenously into nude mice pretreated with cyclophosphamide (in order to depress primarily natural killer activity), several large lung colonies were obtained. Renal localization was also observed. In vitro cultures obtained from tumors or secondaries retained the ability to differentiate in the myogenic pathway shown by the parental cell lines. Intravenous injection into nude mice could therefore constitute an interesting experimental system to study metastatic ability and differentiation properties of human rhabdomyosarcoma cells.

Adrenal Gland Neoplasms↗
PubMed1987

Growth and metastasis in allogeneic hosts. Lack of H-2-negative or somatic hybrid variant selection.

In vitro cultured B16 melanoma cells, which were previously found to have an impaired expression of H-2Kb and Db (as evaluated by antisera absorption assay), were used to study growth and metastasis in allogeneic mice in relation to H-2 expression. The possible emergence of somatic hybrids with host cells was also examined. B16-A cells grown subcutaneously in allogeneic BALB/c mice (H-2d) did not show a lack of H-2b expression, nor the acquirement of H-2d antigens was found. Spontaneous lung metastases were found in about 30% of BALB/c mice with progressing B16 tumor. Single lung metastases showed higher H-2b levels than cells from the respective tumors, and did not express host H-2 antigens. Tumor take was concomitant to the rise of an anti-H-2b humoral response: disease outcome was independent from the serum titer. B16-A cells injected intravenously in BALB/c mice gave rise to lung colonies; different colonies showed a wide range of H-2b antigens levels and no H-2d expression. Lung colonization capacity in normal allogeneic BALB/c mice was significantly higher than in syngeneic C57BL/6 mice. Both syngeneic and allogeneic mice, when pretreated with cyclophosphamide (CY) to reduce natural killer cell activity, showed a significant increase in lung colonization by B16-A cells. CY-treated C57BL/6 mice showed significantly higher numbers of lung colonies than CY-treated BALB/c mice. In conclusion, B16 growth and metastasis in the allogeneic environment do not seem to be determined by a selection of H-2-negative variants or by the emergence of somatic hybrids with host cells.

Animals↗
PubMedDate not supplied

Enhancement of experimental metastatic ability by tumor necrosis factor-alpha alone or in combination with interferon-gamma.

The effects of recombinant tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on B16 mouse melanoma experimental metastatic ability and major histocompatibility complex (H-2b) antigens expression were studied. B16 cells exposed in vitro to TNF-alpha had an increased H-2 expression and were more metastatic than untreated cells. The simultaneous treatment with TNF-alpha and IFN-gamma amplified the enhancement of experimental metastasis and all other effects obtained with TNF-alpha alone. The B16 clone B78H1, selectively resistant to H-2 induction and to enhancement of metastatic ability by IFN-gamma, was not affected by treatment with TNF-alpha and with TNF-alpha + IFN-gamma. These findings contribute to a better understanding of the pleiotropic effects of TNF, some of which can have opposing actions in the complex tumor-host relationships.

Animals↗
PubMedDate not supplied

Impact of IGF-I/IGF-IR circuit on the angiogenetic properties of Ewing's sarcoma cells.

The insulin-like growth factor receptor I (IGF-I)-mediated circuit is a major autocrine loop for Ewing's sarcoma (ES) cells, and plays a role the pathogenesis and malignancy of this tumor. IGF-I receptor (IGF-IR) has emerged as a good therapeutic site for ES patients. In this study, we analyzed the impact of strategies targeting the IGF-IR on the regulation of VEGFs, which are of fundamental importance in angiogenesis, and TGFbeta, CTGF and Cyr61, which are factors primarily involved in skeletal growth control and angiogenesis. IGF-I increases expression of VEGF-A, TGFbeta, CTGF and Cyr61 mRNA. However, only the modulation of VEGF-A expression appears to be mediated by IGF-IR. Functional assays on endothelial cells indicate a strict correlation between survival and proliferation of HUVECs and VEGF-A levels, confirming a major role for this factor in angiogenesis. Blockage of IGF-IR functions by neutralizing antibody or antisense strategies significantly reduced the expression and secretion of VEGF-A by ES cells, and supernatants of treated cells were unable to sustain the survival and proliferation of HUVECs. Analysis of the signaling mechanisms involved in constitutive or IGF-induced expression and secretion of VEGF-A indicated that PI3-K and MAPK signaling pathways are both required for VEGF expression and production in ES cells. Selective inhibitors LY294002 or PD98059 were highly effective in reducing the ability of ES cells to produce VEGF-A and stimulate survival and proliferation of HUVECs. Taken together, these findings add a new activity to the IGF-I repertoire in ES and highlight how disruption of IGF-IR functions may constitute an effective tool for the control of neovascularization in this tumor.

Base Sequence↗
PubMedDate not supplied

Induction of HLA class II antigens in osteosarcoma cells by interferons and tumor necrosis factor alpha.

In this study we have evaluated the ability of interferons (IFNs) alpha, beta, gamma and Tumor Necrosis Factor (TNF) alpha to modulate the expression of the Major Histocompatibility Complex (MHC) antigens in human osteosarcoma cells. The osteosarcoma cell lines Saos-2 and U-2 OS, treated in vitro with IFNs and TNF alpha, showed an increased expression of class I HLA antigens. However, only IFN gamma and, to a lower extent, IFN beta induced the expression of class II HLA antigens. These effects were dose and time-dependent. Simultaneous treatment with IFN gamma and IFN beta or TNF alpha, which by itself was unable to induce the expression of class II HLA antigens, produced different effects on the two osteosarcoma cell lines: in Saos-2 IFN beta and TNF alpha amplified the effects obtained with IFN gamma alone; in U-2 OS, TNF alpha increased the expression induced by IFN gamma on class II HLA antigens, whereas IFN beta antagonized the effects of IFN gamma. IFN alpha did not influence the induction of class II HLA antigens by IFN gamma in the two osteosarcoma cell lines. IFNs have been introduced in some clinical protocols for the treatment of osteosarcoma, based on their antiproliferative activity. Our findings may contribute to a better knowledge of the effects of IFNs and TNF alpha in osteosarcoma by showing the existence of more complex interactions.

Cell Division↗
PubMedDate not supplied

Metastatic ability and differentiative properties of a new cell line of human embryonal rhabdomyosarcoma (CCA).

A new cell line (CCA) was established from a human embryonal rhabdomyosarcoma. It showed an "early" myogenic differentiation pattern: vimentin expression was found in 100% of cells, desmin in about 40% and myosin of the embryonic isoform in about 5%. Class I HLA expression on CCA cells was undeterctable but was greatly increased by in vitro treatment with human recombinant interferon-gamma and only marginally increased by human recombinant tumour necrosis factor-alfa. CCA cell line was tumorigenic in nude mice after either subcutaneous or intramuscular injection; macroscopic spontaneous metastases were not detected. The ability to induce metastatic nodules in the lungs was found when CCA cells were injected intravenously in cyclophosphamide-pretreated nude mice and, at low frequency, in untreated nude mice.

Animals↗
PubMedDate not supplied

Establishment and characterization of multidrug-resistant human osteosarcoma cell lines.

Multidrug resistant variants of two human osteosarcoma cell lines (U-2 OS and Saos-2) were selected by continuous exposure to doxorubicin. The in vitro and in vivo growth characteristics of these sublines as well as the expression of osteoblastic markers and of some surface antigens were analyzed. Resistant variants showed a higher doubling time and a lower cloning efficiency, and a lower metastatic ability after i.v. injection than corresponding parental cell lines. All the sublines showed overexpression of p-glycoprotein (referred to as p170). The level of expression of this protein in the different cell lines was directly related to the degree of resistance as shown by the in vitro sensitivity to doxorubicin and other multidrug-related drugs. In sublines showing the highest levels of resistance (over 300-fold), p170 overexpression was associated with mdr 1 gene amplification. These are the first multidrug resistant human osteosarcoma cell lines ever reported. They may be used as a model for further investigations into the mechanisms of drug resistance in osteosarcoma and as a standard for the assessment of chemosensitivity in clinical samples.

ATP Binding Cassette Transporter, Subfamily B, Mem↗