Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cloned lines of the methylcholanthrene-induced DBA/2 T lymphoma Eb and its highly metastatic variant line ESb were analyzed for differences in the expression of serologically detectable cell surface differentiation markers. Flow cytofluorographic analysis of cells stained with fluorescein isothiocyanate-conjugated monoclonal rate anti-mouse Thy-1, Lyt-1, Lyt-2 and complement-dependent cytotoxicity with mouse alloantisera against Lyt-3.2 and Ly-6.2 revealed, for the parental low metastasizing line, Eb, a phenotype of Thy-1+, Lyt-1-, Lyt-2+, Lyt-3+, Ly-6+, whereas the highly metastasizing variant line typed as Thy-1-, Lyt-1+, Lyt-2-, Lyt-3-, Ly-6-. Analysis of galactose oxidase/NaB3H4-labeled glycoproteins from Eb and ESb clones by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate showed further phenotypic differences. Selective binding of radiolabeled glycoproteins to Helix pomatia or Vicia villosa-Sepharose, respectively, allowed the identification of T130 to be expressed on Eb cells and T145 to be expressed on some ESb clones. The latter antigen is expressed on murine cytotoxic T lymphocytes. Immune precipitation analysis revealed that Eb and ESb bear different molecular forms of the T200 antigen. Comparisons of iodinated surface proteins derived from tumor cells either treated or untreated with tunicamycin indicated that many of the differences in membrane proteins between Eb and ESb cells could be attributed to differences in glycosylation. Our results, derived from a defined tumor system of lymphoid origin, show that the progression from a low to a high malignant tumor line can be associated with changes in the expression of various defined cell surface differentiation antigens. The question of a possible relationship between tumor progression and cell differentiation or dedifferentiation is discussed.
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PMID:Different expression of Lyt differentiation antigens and cell surface glycoproteins by a murine T lymphoma line and its highly metastatic variant. 612 26

Considerable evidence supports a role for polyclonal serum natural Ab (NAb) as a mediator of natural resistance against tumors. However, the molecular mechanisms of this NAb activity are not known. Flow cytometry selection of L5178Y-F9 murine T lymphoma cells for high NAb binding provided the variant LYNAb+, which exhibited an inversely corresponding reduction in tumorigenicity. Accompanying the increased NAb binding, LYNAb+ bound more monoclonal 14.8 anti-CD45RA and DNL-1.9 anti-CD45RC and less 13/2 anti-pan CD45, and the binding of MB23G2 anti-CD45RB was eliminated. However, neuraminidase treatment increased NAb binding and detection of pan CD45, CD45RA, and CD45RC but reduced CD45RB expression, suggesting that the epitopes recognized by the former Abs are masked by sialic acid, while the latter includes sialic acid. Growth of the LYNAb+ from a threshold s.c. inoculum in syngeneic DBA/2 mice yielded more tumorigenic cells which bound less NAb, anti-CD45RA, and anti-CD45RC; the same very low anti-CD45RB; and more anti-pan CD45. In accord with the mAb binding, the L5178Y-F9 and an in vivo passaged LYNAb+ variant expressed predominantly lower m.w. CD45 isoforms while the LYNAb+ expressed predominantly higher 200-kDa isoforms. The consistent correspondence between CD45RA and CD45RC determinant expression, CD45 isoform expression, tumorigenicity, and NAb binding exhibited by T lymphoma cells selected for high NAb binding in vitro or through tumor progression in vivo suggests that asialo high m.w. isoforms of the cell surface-signaling molecule CD45 are differentially expressed during tumor development and furthermore that they participate in NAb-mediated antitumor mechanisms.
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PMID:Differential CD45 isoform expression accompanies reduced natural antibody binding in L5178Y-F9 tumor progression. 920 Apr 72

Abelson murine leukemia virus (A-MuLV) is an acute transforming retrovirus that preferentially transforms early B-lineage cells both in vivo and in vitro. Its transforming protein, v-Abl, is a tyrosine kinase related to v-Src but containing an extended C-terminal domain. Many mutations affecting the C-terminal portion of the molecule block the pre-B-transforming activity of v-Abl without affecting the fibroblast-transforming ability. In this study we have determined the abilities of both wild-type and C-terminally truncated (p90) forms of v-Abl to transform cells from p53(-/-) mice. Lack of p53 increases the susceptibility of bone marrow cells to transformation by v-Abl by a factor of more than 7 but does not alter v-Abl's preference for B220(+) IgM(-) pre-B cells. p53-deficient mice have earlier tumor onset, more rapid tumor progression, and decreased survival time following A-MuLV infection, but all of the tumors are pre-B lymphomas. Thus, p53-dependent pathways inhibit v-Abl transformation but play no role in conferring preferential transformation of pre-B cells. Surprisingly, the C-terminally truncated form of v-Abl (p90) transforms pre-B cells very efficiently in mice lacking p53, thus demonstrating that the C terminus of v-Abl does not determine preB tropism but is necessary to overcome p53-dependent inhibition of transformation.
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PMID:p53 deficiency increases transformation by v-Abl and rescues the ability of a C-terminally truncated v-Abl mutant to induce pre-B lymphoma in vivo. 1061 Dec 41

We describe a case of testicular B cell lymphoma with deletion of chromosome 5, del(5)(p11), as a sole structural abnormality. Histopathological diagnosis of the tumor was a high-grade lymphoma of the diffuse type containing cells positive for B cell specific antigen (CD20) and negative for the leukocyte common antigen (CD45). Deletion 5p may define the region of a tumor suppressor gene that could be associated with tumor progression and invasiveness and may serve as an indicator of poor prognosis in testicular lymphomas.
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PMID:Deletion 5p11 accompanied by multiple numerical changes in testicular lymphoma. 1173 24

At clinical presentation, multiple myeloma (MM) is already a well-established disease. The processes involved in earlier stages are, however, unknown. Here the 5T2MM murine model was used to analyze differentiation, proliferation, invasion, and apoptosis of MM cells during disease progression. Naive mice were injected with 5T2MM cells and from the onset of the experiment 3 mice were killed each week until the end stage. Myeloma cells were isolated from the bone marrow and selected by sequential gating of 5T2MM idiotype(+) cells by flow cytometry. Microscopic analysis of these sorted 5T2MM idiotype(+) cells confirmed their identity as true myeloma cells. Based on serum paraprotein concentration and bone marrow tumor load, 3 disease stages were distinguished: a quiescent stage, an intermediate stage, and an end stage, of slow, moderate, and accelerated tumor progression, respectively. In the quiescent stage, the majority of the myeloma cells were CD45(+)CD138(-)IL-6R alpha(+), corresponding to an immature, invasive, and apoptosis-resistant phenotype. In the end stage the majority of the myeloma cells had differentiated into CD45(-)CD138(+)IL-6R alpha(-) cells, corresponding to a mature, less invasive, and apoptosis-sensitive phenotype. In the intermediate stage a gradual transition from the quiescent toward the end stage was observed. In line with these data, analysis of sorted 5T2MM cells demonstrated a significant decrease in invasive capacity and a significant increase in (dexamethasone-induced) apoptosis sensitivity and in proliferation during the disease progression. These data suggest that myeloma disease progression is a multistage and dynamic process of differentiation, proliferation, invasion, and apoptosis.
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PMID:Multiple myeloma tumor progression in the 5T2MM murine model is a multistage and dynamic process of differentiation, proliferation, invasion, and apoptosis. 1248 Jun 92

Both CD45(+) and CD45(-) multiple myeloma (MM) cells are observed in the bone marrow (BM) of MM patients; however, their impact on the outcome of the disease is unknown. Most (92%) of the mice injected with murine 5T2MM cells develop myeloma in 10-12 weeks and show hind leg paralysis at the end phase of the disease. In the end stage 5T2MM cells are predominantly CD45(-), in analogy to the common human situation. Herein we report that 8% of the mice have a delayed tumor progression (14-24 weeks) with a complete different feature in the end stage of the disease. These animals had typically a bowed back and never got paralyzed. The MM cells in the BM of these mice were predominantly CD45(+). These data indicate that CD45 subsets are associated with the final outcome of myeloma disease.
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PMID:Delayed in vivo disease progression is associated with high proportions of CD45+ myeloma cells in the 5T2MM murine model. 1281 Jun 19

The implantation of small pieces of human primary lung tumor biopsy tissue into SCID mice results in a viable s.c. xenograft in which the tissue architecture, including tumor-associated leukocytes, tumor cells, and stromal cells, is preserved in a functional state. By monitoring changes in tumor volume, gene expression patterns, cell depletion analysis, and the use of function-blocking Abs, we previously established in this xenograft model that exogenous IL-12 mobilizes human tumor-associated leukocytes to kill tumor cells in situ by indirect mechanisms that are dependent upon IFN-gamma. In this study immunohistochemistry and FACS characterize the early cellular events in the tumor microenvironment induced by IL-12. By 5 days post-IL-12 treatment, the constitutively present human CD45(+) leukocytes have expanded and infiltrated into tumor-rich areas of the xenograft. Two weeks post-treatment, there is expansion of the human leukocytes and complete effacement of the tumor compared with tumor progression and gradual loss of most human leukocytes in control-treated xenografts. Immunohistochemical analyses reveal that the responding human leukocytes are primarily activated or memory T cells, with smaller populations of B cells, macrophages, plasma cells, and plasmacytoid dendritic cells capable of producing IFN-alpha. The predominant cell population was also characterized by FACS and was shown to have a phenotype consistent with a CD4(+) effector memory T cell. We conclude that quiescent CD4(+) effector memory T cells are present within the tumor microenvironment of human lung tumors and can be reactivated by the local and sustained release of IL-12 to proliferate and secrete IFN-gamma, leading to tumor cell eradication.
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PMID:Human CD4+ effector memory T cells persisting in the microenvironment of lung cancer xenografts are activated by local delivery of IL-12 to proliferate, produce IFN-gamma, and eradicate tumor cells. 1563 12

Adhesion of inflammatory cells to vascular endothelium is mediated by specific cell adhesion receptors on both leukocytes and endothelial cells. One of the adhesion molecules on the endothelium is P-selectin. Decreased vascular P-selectin expression has been associated with tumor progression in melanoma patients. We now report on the expression of endothelial P-selectin in colorectal cancer (CRC). We studied a colorectal tissue specimen series ranging from normal colorectal tissue via unmetastasized primary tumors to tumors with the same depth of invasion at the primary site but with liver metastases. Moreover, P-selectin expression levels in liver metastases were determined. The number of P-selectin positive vessels as a fraction of the total number of vessels, both intra- and peritumorally, was determined by staining for CD62P and CD34, respectively. Furthermore, by immunostaining for leukocytes (CD45) and macrophages (CD68), it was evaluated whether levels of P-selectin expression influenced infiltrate density and composition. The results showed that levels of peritumoral P-selectin expression were reciprocal to the degree of progression in CRC. This relation was even more pronounced intratumorally: in metastasized primary tumors and in the metastatic lesions, P-selectin expression was virtually absent. This distribution pattern was reflected in the numbers of leukocytes that accumulated in the various tissues, since in the primary tumors with metastases, and in the metastatic lesions, hardly any infiltrating cells were observed. In these lesions, leukocytes were present in the peritumoral zone, but seemed unable to enter the tumor tissue. In primary tumors without metastasis, the intratumoral leukocyte infiltration density was significantly higher. Recruitment levels of macrophages remained constant throughout the different tissues. We suggest that downregulation of endothelial P-selectin expression is a mechanism by which CRC lesions evade inflammatory regression and, thereby, progress to a more advanced stage of malignancy.
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PMID:Progressive loss of endothelial P-selectin expression with increasing malignancy in colorectal cancer. 1564 Aug 34

The contribution of the tumor stroma to cancer progression has been increasingly recognized. We had previously shown that in human neuroblastoma tumors orthotopically implanted in immunodeficient mice, stromal-derived matrix metalloproteinase-9 (MMP-9) contributes to the formation of a mature vasculature by promoting pericyte recruitment along endothelial cells. Here we show that MMP-9 is predominantly expressed by bone marrow-derived CD45-positive leukocytes. Using a series of bone marrow transplantation experiments in MMP-9(+/+) and MMP-9(-/-) mice xenotransplanted with human neuroblastoma tumors, we show that bone marrow-derived MMP-9 is critical for the recruitment of leukocytes from bone marrow into the tumor stroma and for the integration of bone marrow-derived endothelial cells into the tumor vasculature. Expression of MMP-9 by bone marrow-derived cells in the tumor stroma is also critical for the formation of a mature vasculature and coverage of endothelial cells with pericytes. Furthermore, in primary human neuroblastoma tumor specimens of unfavorable histology, we observed a higher level of tumor infiltration with MMP-9 expressing phagocytic cells and a higher degree of coverage of endothelial cells by pericytes when compared with tumor specimens with a favorable histology. Taken together, the data show that in neuroblastoma, MMP-9 plays a critical role in the recruitment of bone marrow-derived cells to the tumor microenvironment where they positively contribute to angiogenesis and tumor progression.
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PMID:The contribution of bone marrow-derived cells to the tumor vasculature in neuroblastoma is matrix metalloproteinase-9 dependent. 1583 51

It is rarely considered that age-related common vascular co-morbidities may affect therapeutic outcomes of antiangiogenic therapy in cancer. Indeed, the accepted model of human disease consists of 4- to 8-week-old (young) tumor-bearing, but otherwise healthy, experimental mice, yet human cancers are diagnosed and treated in later decades of life when atherosclerosis and vascular diseases are highly prevalent. Here we present evidence that tumor growth and angiogenesis are profoundly altered in mice affected by natural aging and with genetically induced atherosclerosis (in ApoE(-/-) mice). Thus, transplantable tumors (Lewis lung carcinoma and B16F1) grew at higher rates in young (4 to 8 weeks old) ApoE(+/+) and ApoE(-/-) nonatherosclerotic syngeneic recipients than in their old (12 to 18 months old) or atherosclerotic (old/ApoE(-/-)) counterparts. These age-related changes were paralleled by reduced tumor vascularity, lower expression of tumor endothelial marker 1, increased acute tumor hypoxia, depletion of circulating CD45(-)/VEGFR(+) cells, and impaired endothelial sprouting ex vivo. Exposure of tumor-bearing mice to metronomic therapy with cyclophosphamide exerted antimitotic effects on tumors in young hosts, but this effect was reduced in atherosclerotic mice. Collectively, our results suggest that vascular aging and disease may affect tumor progression, angiogenesis, and responses to therapy.
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PMID:Atherosclerosis and vascular aging as modifiers of tumor progression, angiogenesis, and responsiveness to therapy. 1782 92


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