Involvement of aberrant DNA methylation on reduced expression of lysophosphatidic acid receptor-1 gene in rat tumor cell lines

2006 ◽  
Vol 349 (3) ◽  
pp. 1151-1155 ◽  
Author(s):  
Toshifumi Tsujiuchi ◽  
Kyoko Shimizu ◽  
Mariko Onishi ◽  
Eriko Sugata ◽  
Hiromasa Fujii ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Tumor Cell ◽  
Cell Lines ◽  
Lysophosphatidic Acid ◽  
Tumor Cell Lines ◽  
Acid Receptor ◽  
Lysophosphatidic Acid Receptor ◽  
Aberrant Dna Methylation ◽  
Rat Tumor

scholarly journals Different Expressions and DNA Methylation Patterns of Lysophosphatidic Acid Receptor Genes in Mouse Tumor Cells

Pathobiology ◽  
2010 ◽  
Vol 77 (6) ◽  
pp. 309-314 ◽  
Author(s):  
Kyoko Okabe ◽  
Mai Hayashi ◽  
Naoko Wakabayashi ◽  
Yasuna Yamawaki ◽  
Miki Teranishi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Tumor Cells ◽  
Lysophosphatidic Acid ◽  
Mouse Tumor ◽  
Acid Receptor ◽  
Lysophosphatidic Acid Receptor ◽  
Methylation Patterns

A Sensitive Molecular Method for Detection of Disseminating Hematopoietic Tumor Cells by Using Specific Epigenetic DNA Methylation Biomarkers

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4850-4850
Author(s):  
Michael X Wang ◽  
Xiaohui Zhao ◽  
Srilatha Nalluri ◽  
Huan-You Wang ◽  
Kristen H. Taylor ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bone Marrow ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Genomic Dna ◽  
Cpg Island ◽  
Lymphoblastic Leukemia ◽  
Single Step ◽  
Tumor Cell Lines

Abstract Background: Most cancer deaths are caused by hematogenous spread and subsequent metastasis. Emerging data indicates that the presence of circulating tumor cells in peripheral blood (CTC) and disseminating tumor cells in bone marrow (DTC) is an early event in tumorigenesis. These circulating or disseminating rare tumor cells may represent a distinct clone with cancer stem cell properties (metastatic stem cells). Clinically, the presence of CTC and DTC is relevant to overt metastases. Early detection and characterization of these rare biologically distinct tumor cells with sensitive and specific methods provide vital information for cancer biology and early clinical intervention and thus improve patients’ survival. Method Design: Genomic DNA was extracted from patient blood, bone marrow aspirate specimens and cancer cell lines prior to digestion with 4 methylation sensitive restriction enzymes. Hypermethylated CpG island regions in tumors, in contrast to their counterpart in normal cells which are completely digested, remain resistant to digestion and therefore can be differentially amplified by PCR. Thus, the specific PCR products on the gel represent the specific methylation loci in the tumor cells in the patient specimens. Results: First, we tested a total of 26 cancer cell lines including 17 hematopoietic tumors and 9 solid tumors. The hematopoietic tumor cell lines represent a spectrum of B-cell malignancies, T-cell lymphoblastic leukemia and acute myeloid leukemia. The solid tumor cell lines represent the major anatomic sites of human carcinoma including lung, colon, breast, prostate, ovarian and skin (melanoma). We found multiple DNA methylation markers specific for lymphoid, myeloid and solid tumors. By using DLC-1 (deleted in liver cancer-1), a tumor suppressor gene, as a single marker, CpG island methylation was detected in 13 out of 17 hematopoietic tumor cell lines (76%) and 6 out of 9 solid tumor cell lines (67%). We then used B-cell acute lymphoblastic leukemia (B-ALL) as a testing case to verify the method in a total of 135 clinical specimens. DLC-1 methylation was detected in 64% and 54% of diagnostic bone marrow aspirates and peripheral blood specimens, respectively, but none was detected in normal or non-leukemic bone marrow or blood control samples. By adding two additional methylation markers PCDHGA12 and CDH1, greater than 90% of B-ALL patients can be detected. We also traced 4 B-ALL cases and 4 follicular lymphoma cases up to 10 years retrospectively and found that the DLC-1 methylation is exactly correlated with patient clinical status. Lastly, by mixing normal and leukemic cell genomic DNA, analytic sensitivity was determined as 0.1% or 10−3 in a single-step PCR and 0.00001% or 10−6 in a nested PCR suggesting that this method is capable of detecting as few as 5 leukemic cells in a single-step PCR. Conclusion: By utilizing tumor specific DNA methylation marker(s), we have developed a simple, highly sensitive and specific gel-based PCR assay, namely Multiple Methylation Sensitive Enzyme Restriction PCR (MSR-PCR) for detection of CTC and DTC from blood and bone marrow of majority of hematopoietic malignancies. The method can potentially be used for early diagnosis and molecular monitoring in vast majority of clinical cancer patients.

scholarly journals Nm23-H1 Suppresses Tumor Cell Motility by Down-regulating the Lysophosphatidic Acid Receptor EDG2

2007 ◽  
Vol 67 (15) ◽  
pp. 7238-7246 ◽  
Author(s):  
Christine E. Horak ◽  
Jong Heun Lee ◽  
Abdel G. Elkahloun ◽  
Mathieu Boissan ◽  
Sylvie Dumont ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Motility ◽  
Lysophosphatidic Acid ◽  
Acid Receptor ◽  
Lysophosphatidic Acid Receptor ◽  
Tumor Cell Motility

scholarly journals Telomere Position Effect and Silencing of Transgenes near Telomeres in the Mouse

2006 ◽  
Vol 26 (5) ◽  
pp. 1865-1878 ◽  
Author(s):  
Mehrdad Pedram ◽  
Carl N. Sprung ◽  
Qing Gao ◽  
Anthony W. I. Lo ◽  
Gloria E. Reynolds ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Tumor Cell ◽  
Cell Lines ◽  
Es Cells ◽  
Position Effect ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Telomere Position Effect

ABSTRACT Reversible transcriptional silencing of genes located near telomeres, termed the telomere position effect (TPE), is well characterized in Saccharomyces cerevisiae. TPE has also been observed in human tumor cell lines, but its function remains unknown. To investigate TPE in normal mammalian cells, we developed clones of mouse embryonic stem (ES) cells that contain single-copy marker genes integrated adjacent to different telomeres. Analysis of these telomeric transgenes demonstrated that they were expressed at very low levels compared to the same transgenes integrated at interstitial sites. Similar to the situation in yeast, but in contrast to studies with human tumor cell lines, TPE in mouse ES cells was not reversed with trichostatin A. Prolonged culturing without selection resulted in extensive DNA methylation and complete silencing of telomeric transgenes, which could be reversed by treatment with 5-azacytidine. Thus, complete silencing of the telomeric transgenes appears to involve a two-step process in which the initial repression is reinforced by DNA methylation. Extensive methylation of the telomeric transgenes was also observed in various tissues and embryonic fibroblasts isolated from transgenic mice. In contrast, telomeric transgenes were not silenced in ES cell lines isolated from 3-day-old preimplantation embryos, consistent with the hypothesis that TPE plays a role in the development of the embryo.

scholarly journals Cancer-associated fibroblast heterogeneity is associated with organ-specific metastasis in pancreatic ductal adenocarcinoma

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xingyi Pan ◽  
Jiaojiao Zhou ◽  
Qian Xiao ◽  
Kenji Fujiwara ◽  
Mengwen Zhang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Liver Metastasis ◽  
Tumor Cell ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Cells ◽  
Cell Lines ◽  
Lung Metastasis ◽  
Ductal Adenocarcinoma ◽  
Tumor Cell Lines ◽  
Organ Specific

Abstract Background Metastasis occurs in the majority of pancreatic ductal adenocarcinoma (PDAC) patients at diagnosis or following resection. Patients with liver metastasis and those with lung metastasis have significantly different prognosis. Here, we sought to understand how cancer-associated fibroblasts (CAFs) play roles in the development of organ-specific metastasis. Methods PDAC tumor cell lines established from the primary tumors with liver and lung metastasis potentials, respectively, in Kras/p53 mutation conditional knock-in (KPC) mice were co-cultured with matched CAFs or mouse mesenchymal stem cells. CAFs were isolated from metastases and subjected to DNA methylation and whole transcriptomic RNA sequencing analysis. Results The ability of mouse PDAC tumor cell lines in developing liver or lung-specific metastases was demonstrated in orthotopic models. Tumor cells associated with liver metastasis potential, but not those associated with lung metastasis potential, induced the methylation of metabolism genes including NQO1 and ALDH1a3 and subsequent downregulated mRNA expression of a broader group of metabolism genes in CAFs. DNA methylation and downregulation of metabolism genes in CAFs in liver metastasis, but not those in lung metastasis, appeared to be regulated by DNA methyltransferase. Tumor cells associated with liver metastasis potential, but not those associated with lung metastasis potential, induce inflammatory CAF (iCAF) signatures. CAFs from liver metastasis demonstrated a more homogenous iCAF phenotype, whereas CAFs from lung metastasis maintained the heterogeneity. Conclusions PDAC with organ-specific metastatic potentials has different capacities in inducing methylation of metabolism genes in CAFs, modulating CAF phenotypes, and resulting in different levels of heterogeneity of CAFs in different metastatic niches.

scholarly journals Regulation of tumor cell – Microenvironment interaction by the autotaxin-lysophosphatidic acid receptor axis

2019 ◽  
Vol 71 ◽  
pp. 183-193 ◽  
Author(s):  
Gabor J. Tigyi ◽  
Junming Yue ◽  
Derek D. Norman ◽  
Erzsebet Szabo ◽  
Andrea Balogh ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Lysophosphatidic Acid ◽  
Acid Receptor ◽  
Lysophosphatidic Acid Receptor ◽  
Cell Microenvironment

Possible involvement of lysophosphatidic acid receptor-5 gene in the acquisition of growth advantage of rat tumor cells

2011 ◽  
Vol 50 (8) ◽  
pp. 635-642 ◽  
Author(s):  
Kyoko Okabe ◽  
Mai Hayashi ◽  
Yasuna Yamawaki ◽  
Miki Teranishi ◽  
Kanya Honoki ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Lysophosphatidic Acid ◽  
Acid Receptor ◽  
Lysophosphatidic Acid Receptor ◽  
Rat Tumor
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