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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interfering with Ets transcription factor function reverses multiple aspects of the transformed phenotype of mouse or human tumor cells. However, the unknown number of individual Ets factors expressed in any cellular context and the similar DNA binding specificities of Ets family members complicates the identification of those that mediate transformation. By utilizing quantitative PCR assays for 25 mouse Ets factors, we analyzed the expression of essentially the entire Ets family in normal mammary tissue, mammary-related cell lines, and mammary tumors. In normal mammary tissue, 24 Ets factors were expressed. Even clonal derived cell lines expressed 14-20 Ets members. The most abundant Ets factor mRNAs measured in normal mammary tissue were Elk4, Elf1, and Ets2. Subtractive analysis of mammary tissue identified which Ets factors were predominantly expressed in the myeloid/lymphoid or epithelial cell compartments. Comparison of Ets factor expression in normal mammary tissue and mammary tumors identified significantly elevated expression of Pse/PDEF, Ese2/Elf5, Ese3/Ehf, TEL/Etv6, and Elf2/NERF in mammary tumors and confirmed previously reported alterations in expression of Ese1/Elf3 and the PEA3 subfamily. Expression of 13 Ets target genes, implicated in various aspects of tumor progression, was also analyzed. Altered expression of particular Ets target genes was significantly correlated with particular Ets factors (e.g. maspin and Ese2), suggesting specific in vivo regulatory roles. Together, this comprehensive analysis revealed unexpectedly diverse Ets family gene expression, characterized novel Ets factor changes in mammary tumors, and implicated specific Ets factors in the regulation of multiple genes involved in mammary tumor progression.
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PMID:Changes in the expression of many Ets family transcription factors and of potential target genes in normal mammary tissue and tumors. 1466 58

DNA polymerase theta (Pol theta) is a recently identified family A polymerase that contains an intrinsic helicase domain. Drosophila Pol theta mutants are hypersensitive to bifunctional DNA crosslinking agents and exhibit an elevated frequency of spontaneous chromosomal aberrations, suggesting a role for Pol theta in repair of DNA interstrand crosslinks and in the general maintenance of genome stability. To investigate a possible involvement of Pol theta in tumorigenesis, we have examined its expression in various normal and malignant tissues. Paired tumor and adjacent nontumorous tissues from patients with lung (n = 27), stomach (n = 28) and colon (n = 26) cancer, as well as 26 normal human tissues, were examined for Pol theta expression by RT-PCR, Northern or Western blot analysis. Pol theta was predominantly expressed in primary lymphoid organs including the fetal liver, thymus and bone marrow where lymphocyte progenitors undergo V(D)J rearrangements of their antigen receptor genes. In addition, Pol theta expression was upregulated in germinal center B cells, in which class switch recombination of the immunoglobulin genes occurs. Examination of Pol theta expression in matched cancer specimens revealed that Pol theta was barely detectable in the nontumorous tissues but was upregulated in 17 of 27 (63%) lung, 11 of 28 (39%) stomach and 20 of 26 (77%) colon cancers. Moreover, patients with high levels of Pol theta expression had a significantly poorer clinical outcome compared with those expressing low levels of Pol theta. These results implicate that Pol theta may have a specialized function in lymphocytes and that its overexpression may contribute to tumor progression.
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PMID:DNA polymerase theta is preferentially expressed in lymphoid tissues and upregulated in human cancers. 1473 62

The central role of T cells in antitumor immunity is well established. However, tumor progression, often seen in the presence of substantial lymphocytic infiltration, suggests that these T cells are not capable of mounting an effective immune response to control tumor growth. Evidence has accumulated that T lymphocytes infiltrating human neoplasms are functionally defective, incompletely activated, or anergic. Therefore, when characterizing the immune competent cells within lymphoid infiltrates of tumors, it is important to assess their activation state. We investigated the expression of two T-cell activation markers, interleukin 2 receptor alpha (CD25) and OX40 (CD134), by immunohistochemistry in primary cutaneous melanoma samples of 76 patients and analyzed it in relation to tumor stage and tumor progression (>5 years follow-up), as well as to patients' survival. We found that the degree of infiltration by CD25(+) and intratumoral OX40(+) lymphocytes showed a tendency to decrease in thicker melanomas. The frequency of samples with high numbers of peritumoral CD25(+) and OX40(+) cells was significantly lower (P = 0.0009 and P = 0.0087, respectively) in melanomas developing distant visceral metastases, compared with nonmetastatic or lymph node metastatic tumors. For both activation markers studied, high peritumoral densities were associated with longer survival by univariate analysis (P = 0.0028 and P = 0.0255 for CD25 and OX40, respectively), whereas peritumoral OX40(+) lymphocyte infiltration had an impact on survival also in multivariate analysis (P = 0.035). The results suggest that the presence of lymphocytes expressing the T-cell activation markers CD25 or OX40 shows correlation with tumor progression as well as with patients' survival in cutaneous malignant melanoma.
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PMID:T-cell activation marker expression on tumor-infiltrating lymphocytes as prognostic factor in cutaneous malignant melanoma. 1476 73

Although tumor-specific CD8 T-cell responses often develop in cancer patients, they rarely result in tumor eradication. We aimed at studying directly the functional efficacy of tumor-specific CD8 T cells at the site of immune attack. Tumor lesions in lymphoid and nonlymphoid tissues (metastatic lymph nodes and soft tissue/visceral metastases, respectively) were collected from stage III/IV melanoma patients and investigated for the presence and function of CD8 T cells specific for the tumor differentiation antigen Melan-A/MART-1. Comparative analysis was conducted with peripheral blood T cells. We provide evidence that in vivo-priming selects, within the available naive Melan-A/MART-1-specific CD8 T-cell repertoire, cells with high T-cell receptor avidity that can efficiently kill melanoma cells in vitro. In vivo, primed Melan-A/MART-1-specific CD8 T cells accumulate at high frequency in both lymphoid and nonlymphoid tumor lesions. Unexpectedly, however, whereas primed Melan-A/MART-1-specific CD8 T cells that circulate in the blood display robust inflammatory and cytotoxic functions, those that reside in tumor lesions (particularly in metastatic lymph nodes) are functionally tolerant. We show that both the lymph node and the tumor environments blunt T-cell effector functions and offer a rationale for the failure of tumor-specific responses to effectively counter tumor progression.
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PMID:Effector function of human tumor-specific CD8 T cells in melanoma lesions: a state of local functional tolerance. 1508 5

Here we describe a new mouse model with constitutive expression of the catalytic subunit of telomerase (Tert) targeted to thymocytes and peripheral T cells (Lck-Tert mice). Two independent Lck-Tert mouse lines showed higher incidences of spontaneous T-cell lymphoma than the corresponding age-matched wild-type controls, indicating that constitutive expression of Tert promotes lymphoma. Interestingly, T-cell lymphomas in Lck-Tert mice were more disseminated than those in wild-type controls and affected both lymphoid and nonlymphoid tissues, while nonlymphoid tissues were never affected with lymphoma in age-matched wild-type controls. Importantly, these roles of Tert constitutive expression in promoting tumor progression and dissemination were independent of the role of telomerase in telomere length maintenance, since telomere length distributions on a single-cell basis were identical in Lck-Tert and wild-type thymocytes. Finally, Tert constitutive expression did not interfere with telomere capping in Lck-Tert primary thymocytes, although it resulted in greater chromosomal instability upon gamma irradiation in Lck-Tert primary lymphocytes than in controls, suggesting that Tert overexpression may interfere with the cellular response to DNA damage.
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PMID:Constitutive expression of tert in thymocytes leads to increased incidence and dissemination of T-cell lymphoma in Lck-Tert mice. 1512 48

CD10 antigen is a 100-kDa-cell surface zinc metalloendopeptidase expressed in a variety of normal and neoplastic lymphoid and nonlymphoid tissues including melanomas. It was recently shown that metastatic melanomas express more CD10 than primary tumors. We evaluated CD10 expression in tumor and stromal cells in 70 biopsies with primary and 28 with metastatic malignant melanomas. Ki-67, Bcl-2, and Bax were also examined to investigate whether CD10 expression is associated with tumor proliferation index or factors of apoptosis. Formalin-fixed/paraffin-embedded tissues were studied by immunohistochemistry. More advanced primary tumors had higher CD10 expression in the tumor cells (r = 0.27, P = 0.03 for Clark levels and r = 0.29, P = 0.02 for Breslow) and higher Ki-67 proliferation fraction (r = 0.32, P = 0.007 for Clark levels and r = 0.32, P = 0.001 for Breslow). Similarly, CD10 expression in the intratumoral stromal cells was also higher in primary tumors with higher Clark level (P = 0.04, linear-by-linear association) and tumor thickness according to Breslow (r = 0.33, P = 0.01). The presence of CD10+ peritumoral stromal cell cuffs was also positively associated with tumor thickness according to Breslow (r = 0.27, P = 0.05). Also, expression of CD10 and Ki-67 were significantly higher in metastatic than in primary tumors (P = 0.01 and 0.02 respectively), but Bcl-2 expression was higher in primary melanomas (P = 0.02). We conclude that CD10 expression in malignant melanoma is associated with tumor progression.
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PMID:CD10 protein expression in tumor and stromal cells of malignant melanoma is associated with tumor progression. 1520 82

Chemokines represent a large family of polypeptide signaling molecules that are notable for their role in chemotaxis, leukocyte homing, and directional migration. Recent observations have indicated that the expression of chemokine receptors on cancer cells may play a role in tumor progression and metastasis. In this study, the expression of mRNA for chemokine receptors in various human tumor cell lines was analyzed by multiplex-polymerase chain reaction (M-PCR). Strong expression of CCR6 mRNA in 3 of 3 hepatoma cell lines was observed. In the 3 pancreatic cancer cell lines, no specific expression of chemokine receptors was observed. Raji (lymphoma cell line) strongly expressed CCR7 and CXCR4. We further investigated CCR6 mRNA expression in these cell lines by real-time quantitative-PCR. Similar results were obtained by both the PCR methods. Because human liver constitutively express liver and activation-regulated chemokine (specific ligand for CCR6), hepatoma cells may selectively root and spread in the liver. Strong CCR7 and CXCR4 expressions in the lymphoma cell may explain the organ specificity of lymphoma for lymphoid organs as well. These findings probably indicate that some cancer cells have organ specificity via expression of chemokine receptors.
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PMID:[mRNA expression of chemokine receptors in hepatic and pancreatic tumor cell lines]. 1533 56

We describe three lymphoid tumors with the same immunophenotype characteristic for chronic lymphoid leukemia (CD19+/CD5+, clonality of the light immunoglobulin chains, CD23+ and CD10-). However, clinical picture and morphology of neoplastic cells dictate different clinical forms of these cases: chronic lymphoid leukemia, large cell transformation of chronic lymphoid leukemia and diffuse large B-cell lymphoma. Taking into account that immunophenotype reflects the origin of tumor, while clinical outcome and morphological features of cells reflect the stage of tumor progression and/or pathway of tumor formation, we discuss the approach to natural classification of lymphoid tumors based on the process of their evolution.
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PMID:[Comparative characteristics of immunological, clinical and morphological features of human lymphoid tumors in respect with tumor genesis and progression]. 1533 26

The effectors of mucosal and natural immunity (i.e. natural killer, NK, cells and NKT lymphocytes) are known to play an important role in host defence against tumors. Gammadelta T lymphocytes are the most represented cell populations in mucosal associated lymphoid tissue and share several characteristics of T and NK cells. Two main subsets of gammadelta T cells are known: one, expressing the Vdelta2 T cell receptor (TCR), is found in the peripheral blood, while T cells expressing Vdelta1 TCR are resident in epithelial tissues. The former subset is capable of killing myeloma and Burkitt lymphoma cells, while the latter has been implied in the defence against epithelial cancers. Furthermore, there is increasing evidence that alphabeta and gammadelta T lymphocytes make distinct contributions to anticancer surveillance. Indeed, unlike alphabeta T cells, gammadelta T lymphocytes are involved in the recognition of antigens that do not undergo the conventional major histocompatibility complex (MHC)-driven antigen presentation. Down-regulation of expression of MHC alleles as well as tumor-specific antigens is observed frequently during tumor progression, resulting in an impairment of MHC-restricted, alphabeta-T-cell-mediated tumor-specific immunity. Given the unique set of antigens recognized and the lack of requirement for classical antigen-presenting molecules, gammadelta T lymphocytes might, therefore, represent a useful and potent system in anti-cancer surveillance, as proposed for the immune response against pathogens. Evidence that gammadelta and alphabeta cells make distinct contribution to anti-cancer surveillance have been recently provided in mice. Here, we discuss the potential role played by resident Vdelta1+ and circulating Vdelta2+ T lymphocytes in the defense against solid tumors and hematological malignancies.
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PMID:Role of gammadelta T lymphocytes in tumor defense. 1535 83

The mucin-type glycoprotein podoplanin is specifically expressed by lymphatic but not blood vascular endothelial cells in culture and in tumor-associated lymphangiogenesis, and podoplanin deficiency results in congenital lymphedema and impaired lymphatic vascular patterning. However, research into the biological importance of podoplanin has been hampered by the lack of a generally available antibody against the human protein, and its expression in normal tissues and in human malignancies has remained unclear. We generated a human podoplanin-Fc fusion protein and found that the commercially available mouse monoclonal antibody D2-40 specifically recognized human podoplanin, as assessed by enzyme-linked immunosorbent assay and Western blot analyses. We found that, in addition to lymphatic endothelium, podoplanin was also expressed by peritoneal mesothelial cells, osteocytes, glandular myoepithelial cells, ependymal cells, and by stromal reticular cells and follicular dendritic cells of lymphoid organs. These findings were confirmed in normal mouse tissues with anti-podoplanin antibody 8.1.1. Podoplanin was also strongly expressed by granulosa cells in normal ovarian follicles, and by ovarian dysgerminomas and granulosa cell tumors. Although podoplanin was primarily absent from normal human epidermis, its expression was strongly induced in 22 of 28 squamous cell carcinomas studied. These findings suggest a potential role of podoplanin in tumor progression, and they also identify the first commercially available antibody for the specific staining of a defined lymphatic marker in archival human tissue sections, thereby enabling more widespread studies of tumor lymphangiogenesis in human cancers.
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PMID:Up-regulation of the lymphatic marker podoplanin, a mucin-type transmembrane glycoprotein, in human squamous cell carcinomas and germ cell tumors. 1574 2


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