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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clonal growth of cell lines from some human solid tumours can be stimulated by haematopoietic growth factors such as recombinant human (rh) interleukin-3 (IL-3) and rh granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro. Among these cell lines are the human colorectal adenocarcinoma cell line HTB 38 and the human small-cell lung cancer cell line HTB 119. Here we report on a series of experiments studying the influence of subcutaneously administered rhIL-3 and rhGM-CSF on the in vivo growth of HTB 38 and HTB 119 cell lines as xenografts in athymic nu/nu BALB/c mice. Beginning 1 day after transplantation of the tumour the cytokines were administered daily for 20 days as a subcutaneous bolus distant from the tumour lesion at dose levels up to 1 mg/m2/day. The cytokines caused no significant and reproducible growth modulation of the tumours in vivo.
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PMID:Effect of interleukin-3 and granulocyte-macrophage colony-stimulating factor on growth of xenotransplanted human tumour cell lines in nude mice. 131 97

We report on a 67-year-old man with Felty's syndrome (FS) complicated by recurrent pneumonia and an infected wound, which was not healing in spite of maximal antibiotic and local therapy. Encouraged by previous experience, we treated him with granulocyte-macrophage colony-stimulating factor (GM-CSF). His total leukocyte count rose, but the patient's pneumonia deteriorated. In addition, a previously known chronic obstructive lung disease (COLD) was exacerbated acutely. These complications finally led to his death. Postmortem examination revealed widespread pneumonia with invasive aspergillosis and a peripheral adenocarcinoma in his left lung.
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PMID:Treatment of neutropenia in Felty's syndrome with granulocyte-macrophage colony-stimulating factor--hematological response accompanied by pulmonary complications with lethal outcome. 145 82

The effects of human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) 1-1000 U/ml on the growth of human lung cancer cell lines have been studied in vitro. A panel of 10 small cell, 1 adenocarcinoma and 1 large cell lines was used with multidrug resistant sublines of 3 of the panel. The MTT assay was used to quantify cell numbers after 6-8 days' growth in the presence of GM-CSF. Neither growth inhibition nor stimulation of any of the cell lines in the presence of GM-CSF was observed. Any effects of this agent on residual tumour cells may not therefore present a problem during its clinical use to stimulate marrow regeneration after high-dose chemotherapy for lung cancer.
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PMID:Failure of GM-CSF to influence the growth of small cell and non-small cell lung cancer cell lines in vitro. 184 14

We studied the influence of recombinant human (rh) interleukin-3 (IL-3) and rh granulocyte-macrophage colony-stimulating factor (GM-CSF) on the clonal growth of a human colorectal adenocarcinoma cell line in a methylcellulose assay for colony growth of solid tumor cell lines (HTCAMC) and a capillary modification of a human tumor cloning assay in agar (HTCAcap). Both growth factors stimulated the clonal growth of this cell line in a dose-dependent fashion. Neutralizing the monoclonal antibody abolished the effect of rhGM-CSF. There was an inverse correlation between the spontaneous plating efficacy (PE) of the cells and their susceptibility to the stimulation by the growth factors. From day 4 to 7 we found conditions in which clusters and colonies occurred preferentially in the growth factor-stimulated cultures. Single colonies taken from these cultures grew rapidly into macroscopically visible tumors in liquid cultures and had a high secondary PE (PE2) in the HTCAcap, both presenting an argument against a differentiating effect of the growth factors on this tumor cell line. Furthermore, we were able to define conditions in which rhGM-CSF significantly increased the cytotoxicity of 5-fluorouracil (5-FU). However, this effect was dependent on spontaneous PE of the cells, degree of stimulation by the factor, degree of cytotoxicity of 5-FU in the controls, as well as the therapeutic regimen. Since there were only narrow margins for a beneficial effect of rhGM-CSF in this setting when absolute numbers of surviving colonies were counted, it remains doubtful whether this approach will be exploitable in the clinical situation.
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PMID:Stimulation of clonal growth of human colorectal tumor cells by IL-3 and GM-CSF. Modulation of 5-FU cytotoxicity by GM-CSF. 209 80

Using an immunogenic nonmetastatic murine mammary adenocarcinoma (D1-DMBA-3) induced in BALB/c mice by dimethylbenzanthracene, we have previously shown that splenocytes from tumor bearers have depressed lymphocyte responses to mitogens and antigens, including tumor-associated antigens. In addition, they display decreased natural killer and T-cell cytotoxic activities. Macrophages from tumor-bearing mice appear to be responsible for the suppression of T- and B-cell responses to concanavalin A, lipopolysaccharide, and tumor-associated antigens observed in tumor bearers. The appearance of these macrophages in the spleen tightly parallels the progressive growth of the tumor and the concomitant immunosuppression. Simultaneously high levels of macrophage progenitors were observed in blood, bone marrow, lung, and liver. A significant increase of colony-stimulating activity of the granulocyte-macrophage lineage was detected in the sera from tumor-bearing mice. Higher levels of this colony-stimulating activity (CSA) were detected in tumor cystic fluid as compared with the levels in serum. A tumor cell line established in vitro from the D1-DMBA-3 in vivo tumor produces high levels of a factor with CSA in culture supernatant fluids. Partial purification of the CSA from the tumor cell line supernatants was achieved using CentriCell ultrafiltration and SephacrylS-300 chromatography. These studies revealed that the molecular weight of the colony-stimulating-like factor is 32,000 to 35,000. The morphology of the colonies obtained in cultures using this factor is similar to that of the colonies that develop in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) but not with macrophage colony-stimulating factor (M-CSF). CSA from tumor cell supernatants was neutralized by antiserum to GM-CSF but not with anti-M-CSF or anti-granulocyte colony-stimulating factor (G-CSF). Macrophages from bone marrow or peritoneal exudates from normal mice cultured with tumor supernatant for 2 to 3 days strongly inhibit normal splenocyte responses to concanavalin A and lipopolysaccharide. The data suggest that the tumor releases a GM-CSF that alters the hemopoietic system and induces or expands macrophages, which exert a suppressive function on the immune system of tumor-bearing mice.
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PMID:Expansion of immunoregulatory macrophages by granulocyte-macrophage colony-stimulating factor derived from a murine mammary tumor. 213 4

We have studied the effect of recombinant human hematopoietic growth factors (interleukin-3 [rhIL-3], granulocyte-macrophage colony-stimulating factor [rhGM-CSF], and granulocyte CSF [rhG-CSF]) on the clonal growth of human colon adenocarcinoma cell lines HTB-38, CCL 187, and WiDr (CCL 218). The factors stimulated clonal growth of HTB-38 and CCL 187 in a capillary modification of the human tumor clonogenic assay in agar up to twofold. There were dose-response correlations over a range of 1 to 10,000 U/mL for rhIL-3, rhGM-CSF, and rhG-CSF. Incubation with neutralizing monoclonal antibodies abolished the stimulation of clonal growth by rhGM-CSF. The WiDr cell line was nonresponsive to rhIL-3 and rhGM-CSF. These results represent the first evidence that a variety of hematopoietic growth factors can stimulate the growth of clonogenic cells of some nonhematopoietic malignant cell lines in vitro.
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PMID:Various human hematopoietic growth factors (interleukin-3, GM-CSF, G-CSF) stimulate clonal growth of nonhematopoietic tumor cells. 267 1

The ability of malignant cells to respond to growth factor(s) present in or secreted by a distant target organ may be important in tumor metastasis. We used metastatic cell lines and clones of the rat 13762NF mammary adenocarcinoma that show reproducible spontaneous metastatic behavior from the mammary fat pad to regional lymph nodes and lung sites. Whereas poorly lung metastatic MTPa and MTC cells did not grow in response to lung-conditioned medium, highly lung-metastatic MTLn3 cells responded and grew rapidly in lung-conditioned medium. The major growth-promoting factor for MTLn3 cells from porcine and rat lung-conditioned media was purified by using hydroxylapatite affinity and anion exchange chromatography, chromatofocusing, size exclusion chromatography, and preparative native gel electrophoresis. The activity in each of the purification fractions was measured by determining their ability to increase the number of MTLn3 cells in serum-deprived culture. The major component that differentially stimulated the growth of highly metastatic MTLn3 cells was a glycoprotein of Mr approximately 66,000. Under reducing conditions, its apparent Mr was approximately 72,000. This lung-derived mitogen was stable at pH 4.0-9.0, possessed a pI of 6.9-7.0, and preferentially promoted the growth of lung-metastasizing tumor lines over their poorly lung-metastasizing counterparts in rat 13762NF mammary adenocarcinoma and murine B16 melanoma tumor systems. The activity of porcine lung-derived growth factor was not affected by pretreatment with antisera to porcine insulin, human granulocyte-macrophage colony-stimulating factor, human platelet-derived growth factor, or murine epidermal growth factor. It was inactivated by reduction with dithiothreitol or exposure to high temperature (95 degrees C). The results suggest that specific organ-derived growth factors are important in metastatic colonization and organ growth of particular malignant cells.
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PMID:Purification and some properties of a lung-derived growth factor that differentially stimulates the growth of tumor cells metastatic to the lung. 254 64

A case of pancreatic carcinoma associated with marked eosinophilia is reported. A 71-yr-old man was admitted to hospital because of melena and abdominal pain. The systematic examinations revealed pancreatic adenocarcinoma with multiple metastases (rectum, lung and brain). The leukocyte count was gradually increased and reached up to 81.7 X 10(9)/l, of which 54% consisted of eosinophils. Colony-stimulating factor (CSF) was detected both in the patient's serum and in the tumor extracts by a normal human bone marrow culture system. The colonies which were stimulated with patient's serum largely consisted of granulocyte, granulocyte/macrophage and eosinophil types. These results suggest that blood leukocytosis and eosinophilia were due to a high concentration of plasma CSF, which was probably produced by the tumor cells.
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PMID:Pancreatic carcinoma associated with marked eosinophilia: a case report. 350 Aug 71

Circulating neutrophil (polymorphonuclear leukocyte levels rise 50-fold in 13762NF tumor-bearing rats in proportion to the tumor's metastatic potential. Purified tumor-elicited neutrophils enhance metastasis of syngeneic tumor cells when co-injected intravenously; however, circulating and phorbol ester-activated polymorphonuclear neutrophils do not. The purpose of this study was to elucidate the source of tumor-elicited neutrophils in metastatic tumor-bearing rats. We examined the bone marrow in rats bearing tumors of poorly, moderately, and highly metastatic cell clones. Marrow from rats with highly metastatic tumors had increased cellularity (100%), myeloid to erythroid ratio (10:1), and megakaryocytes compared with control rats (cellularity, approximately 80%; myeloid to erythroid ratio, 5:1), with marrows from rats with moderately metastatic tumors having intermediate values. This suggested production of a colony-stimulating factor by the metastatic cells. To confirm this, bone marrow colony formation from control and tumor-bearing rats was compared. Colony number increased in proportion to the metastatic potential of the tumor. Conditioned medium from metastatic cells supported growth of the granulocyte-macrophage colony-stimulating factor/interleukin-3-dependent 32Dcl3 cell line, but media from nonmetastatic or moderately metastatic cells did not. Antibodies to murine granulocyte-macrophage colony-stimulating factor neutralized 32Dcl3 growth in tumor cell conditioned medium. These results suggest production of a granulocyte-macrophage colony-stimulating factor or interleukin-3-like activity by highly metastatic 13762NF clones and implicate a possible role for colony-stimulating factors in regulating the metastatic potential of mammary adenocarcinoma cell clones.
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PMID:Highly metastatic 13762NF rat mammary adenocarcinoma cell clones stimulate bone marrow by secretion of granulocyte-macrophage colony-stimulating factor/interleukin-3 activity. 749 92

The possibility that production of some cytokines in the carcinoma microenvironment is associated with the presence and differentiation of cells belonging to the dendritic cell (DC)/Langerhans' cell (LC) lineage was investigated. Immunohistochemical examination showed the presence of intraepithelial LCs (CD1a- and S100-positive cells) in 6 of 10 squamous cell carcinomas and in 8 of 10 adenocarcinomas. Langerhans' cells were mainly located close to lymphoid aggregates. In situ hybridization performed in four cases (three LC positive and one LC negative) of squamous cell carcinoma and in five cases (four LC positive and one LC negative) of adenocarcinoma showed that some mononuclear cells in the interstitium displayed hybridization with granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF alpha), and interleukin 1-beta (IL1 beta) cDNA probes. Only in LC-positive carcinomas did epithelial cells close to lymphoid aggregates display small amounts of GM-CSF and TNF alpha mRNA expression. Immunohistochemical analysis performed in the 20 cases of lung carcinoma showed that epithelial cells in tumors with lymphoid aggregates and LCs were immunoreactive with antihuman GM-CSF monoclonal antibody. Specimens negative for GM-CSF contained very few LCs. Northern blot analysis was used to investigate GM-CSF, TNF alpha, IL1 alpha, and IL1 beta mRNA expression in six human lung carcinoma cell lines. A constitutive expression of TNF alpha mRNA was found in all of them, whereas only three showed a low constitutive expression of GM-CSF mRNA. In the latter three cell lines treatment with phytohemagglutinin (PHA)-stimulated peripheral blood lymphocyte (PBL) supernatant (PHA-SUP) upregulated GM-CSF mRNA expression and induced that of IL1 alpha mRNA. Carcinomatous epithelial cells producing small amounts of cytokines could promote the recruitment of cells of DC/LC lineage. Subcellular factors produced by reactive lymphocytes and/or macrophages may influence the production of GM-CSF and IL1 alpha by various epithelia. Up-regulation of this production could favor the arrival and differentiation of DCs and activate LC functions.
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PMID:Role of cytokines in distribution and differentiation of dendritic cell/Langerhans' cell lineage in human primary carcinomas of the lung. 763 48


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