Gene Expression Profiling of Metastatic and Nonmetastatic Colorectal Cancer Cell Lines

Futschik, Matthias E.; Jeffs, Aaron; Kasabov, Nikola; Sullivan, Michael; Merrie, Arend E. H.; Reeve, Anthony E.

doi:10.1166/gl.2002.005

Cited by 31 publications

(24 citation statements)

References 46 publications

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“…Tumor metastasis is a major cause of concern and is frequently associated with morbidity and mortality. The metastatic cell line SW-620 was used in our study as a model system for identifying genes with a potential role in colorectal metastasis (Futschik et al, 2002). Most of the tumors, including those of CRC, progress using a variety of enzyme systems, where these multipotent enzymes interact with the extracellular matrix and basement membrane.…”

Section: Discussionmentioning

confidence: 99%

S-adenosylmethionine, a methyl donor, up regulates tissue inhibitor of metalloproteinase-2 in colorectal cancer

Hussain

Khan²,

Shahid³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. DNA methylation is a fundamental epigenetic mechanism in regulating the expression of genes controlling crucial cell functions in cancer development. Gene silencing via CpG island methylation/ demethylation in the promoter region is one of the mechanisms by which different genes are inactivated/activated in human cancers. Tissue inhibitor of metalloproteinase-2 (TIMP-2) is known to antagonize matrix metalloproteinase (MMP) activity and to suppress tumor growth, angiogenesis, invasion, and metastasis. TIMP-2 expression has been found to be both upregulated and downregulated in various cancers. The inconsistent TIMP-2 expression and unclear epigenetic regulation lead us to investigate its role in colorectal cancer in the presence of a methylating Hypomethylation status of tissue inhibitor of metalloproteinase agent. Highly invasive human colorectal cells SW-620 were treated with the methyl donor S-adenosylmethionine (SAM) and its effect was evaluated by cell proliferation, cell cycle, invasion and migration assay. The ability of SAM to down regulate a panel of activated prometastatic, angiogenesis and growth-and cell cycle-regulatory genes was evaluated using end-point and real-time PCR. Treatment of SW-620 with SAM diminished cell proliferation and altered cell cycle kinetic G 2 /M phase cell cycle arrest. An in vitro matrigel invasion assay of SAM-treated cells showed a significant reduction in the invasive potential compared to untreated SW-620 cells. Treatment of SW-620 cells with SAM resulted in activation of TIMP-2 and inhibition of the expression of genes such as MMP (MMP-2, MT1-MMP), urokinase plasminogen activator, and vascular endothelial growth factors. The level of expression of tumor suppressor and apoptotic genes was not significantly higher compared to the untreated control. No changes in the levels of expression of genes (growth and cell cycle regulator), such as TGF-β, Smad2, Smad4, and p21 were observed. Our data support the hypothesis that TIMP-2, along with other prometastatic genes, is hypomethylated and expressed differently in colorectal cancer. Further in-depth analysis is warranted to confirm the promoter region CpG methylation pattern of the TIMP-2 gene.

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Section: Discussionmentioning

confidence: 99%

S-adenosylmethionine, a methyl donor, up regulates tissue inhibitor of metalloproteinase-2 in colorectal cancer

Hussain

Khan²,

Shahid³

et al. 2013

Genet. Mol. Res.

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“…11 RPL8 RNA is overexpressed in metastatic versus primary carcinomas (19). In light of the ubiquitous expression of RPL8 RNA (Table 1), it was surprising that some, but not all, tumor cell lysates derived from different patients stimulated proliferation of Th35-1A (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…Using this approach, we have cloned RPL8, which is shared by melanomas (this study and ref. 7), gliomas (7), colorectal carcinomas (19), and ovarian carcinomas (20).…”

Section: Discussionmentioning

confidence: 99%

Shared MHC Class II–Dependent Melanoma Ribosomal Protein L8 Identified by Phage Display

et al. 2007

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Antigens recognized by T helper (Th) cells in the context of MHC class II molecules have vaccine potential against cancer and infectious agents. We have described previously a melanoma patient's HLA-DR7-restricted Th cell clone recognizing an antigen, which is shared among melanoma and glioma cells derived from various patients. Here, this antigen was cloned using a novel antigen phage display approach. The antigen was identified as the ribosomal protein L8 (RPL8). A peptide of RPL8 significantly stimulated proliferation and/or cytokine expression of the Th cell clone and lymphocytes in four of nine HLA-DR7 + melanoma patients but not in healthy volunteers. The RPL8 antigen may represent a relevant vaccine target for patients with melanoma, glioma, and breast carcinoma whose tumors express this protein. [Cancer Res 2007;67(8):3555-9]

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“…Thus, the different characteristics between SW620 and SW480 cells may contribute to synergistic effects of DAC although SW620 and SW480 cells are derived from same patients. 18) Demethylating agents (DNMT inhibitors) and HDAC inhibitors act through the inhibition of enzymatic activities such as DNMTs and HDACs, respectively. The well-known DNMT inhibitors are DAC and AC, while limited data are available for Zeb.…”

Section: Discussionmentioning

confidence: 99%

Different Schedule-Dependent Effects of Epigenetic Modifiers on Cytotoxicity by Anticancer Drugs in Colorectal Cancer Cells

Hosokawa

Tanaka

Iwakawa

2017

Biological & Pharmaceutical Bulletin

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Limited information is currently available on how to apply epigenetic modifiers to current colorectal cancer (CRC) chemotherapy. The purpose of this study is to clarify the schedule-dependent effects of combined treatment with conventional anticancer drugs and epigenetic modifiers in human CRC cells. Cytotoxicity in 4 CRC cell lines (SW480, HT29, SW48, and HCT116) was measured using the WST-8 assay. As epigenetic modifiers, 3 DNA methyltransferase (DNMT) inhibitors such as decitabine (DAC), azacytidine (AC), and zebularine (Zeb), and 3 histone deacetylase (HDAC) inhibitors including trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), and valproic acid (VPA) were used. Combination effects were analyzed by the isobologram method. SW480 cells showed the lowest sensitivity to the anticancer drugs 5-fluorouracil, SN-38 (the active form of irinotecan), and oxaliplatin. In SW480 cells, epigenetic modifiers other than VPA showed the most significant synergistic effects when used before anticancer drugs, while VPA showed synergistic effects in co-or post-treatment. In the 3 other CRC cells, synergistic effects were less frequent and weaker. The dose of anticancer drugs may be reduced by combining epigenetic modifiers in SW480 cells, which are less sensitive to anticancer drugs, unlike the more sensitive HT29, SW48, and HCT116 cell lines. These results provide useful information for understanding how to incorporate epigenetic modifiers into current CRC chemotherapy.Key words schedule-dependent treatment; epigenetic therapy; colorectal cancer; DNA methyltransferase inhibitor; histone deacetylase inhibitor Epigenetic alterations such as DNA methylation and histone modifications have been identified as a crucial driving force in the initiation and progression of cancer.1) Since epigenetic alterations are reversible, epigenetic modifiers may be beneficial in chemotherapy.2) Several epigenetic modifiers including DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors have been approved by U.S. Food and Drug Administration (FDA) for the treatment of cancer.Combined chemotherapy, including 5-fluorouracil (5-FU) and either irinotecan (CPT-11) or oxaliplatin (L-OHP), has improved the survival period of metastatic colorectal cancer (CRC). However, resistance to these anticancer drugs, which limits the effectiveness of chemotherapy, has been reported. 3,4) In order to overcome this issue, novel combination therapy using epigenetic modifiers is expected. Clinical trials on combination therapy have been performed using solid tumors including CRC.5,6) However, there is not enough integrated information on how to apply epigenetic modifiers to current CRC chemotherapy. We previously reported that a co-treatment with decitabine (DAC, 5-aza-2′-deoxycytidine), a DNMT inhibitor, and L-OHP exerted the most potent synergistic effects among the combinations tested using 5 epigenetic modifiers and 5-FU, CPT-11, or L-OHP in 4 different CRC cell lines. 7)The treatment schedule is important for effective cancer ...

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Gene Expression Profiling of Metastatic and Nonmetastatic Colorectal Cancer Cell Lines

Cited by 31 publications

References 46 publications

S-adenosylmethionine, a methyl donor, up regulates tissue inhibitor of metalloproteinase-2 in colorectal cancer

S-adenosylmethionine, a methyl donor, up regulates tissue inhibitor of metalloproteinase-2 in colorectal cancer

Shared MHC Class II–Dependent Melanoma Ribosomal Protein L8 Identified by Phage Display

Different Schedule-Dependent Effects of Epigenetic Modifiers on Cytotoxicity by Anticancer Drugs in Colorectal Cancer Cells

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