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Cyclooxygenase 2 modulates killing of cytotoxic T lymphocytes by colon cancer cells.

Wang Q, Takei Y, Kobayashi O, Osada T, Watanabe S - J Clin Biochem Nutr (2009)

Bottom Line: Treatment with NS398 resulted in reduction of expression of FasL and TRAIL in HCA7 cells, whereas NS398 did not affect the expression of FasL and TRAIL in HCT116 cells.The number of viable Jurkat cells was diminished when cells were co-cultured with naive, non-pretreated HCA7 or HCA116 cells.In contrast, pretreatment with NS398 failed to inhibit the HCT116-induced Jurkat cell killing.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.

ABSTRACT
Although anti-cancer effects of cyclooxygenase 2 (COX2) inhibitors have been reported, most studies focused on the direct effects of COX2 inhibiters on colon cancer cells. On the other hand, several types of cancers express Fas ligand (FasL) and/or TRAIL and mediate apoptosis of T cells in vitro. The "counter-attack" machinery may account for the mechanisms by which tumors evade host immune surveillance. In this study we determined if COX2 inhibitor could modulate effector molecules of cell death on colon cancer cells changing their effects on cytotoxic T lymphocytes. Colon adenocarcinoma cells, HCA7 and HCT116, the former COX2-positive and the latter COX2-negative, were pre-incubated with/without a COX2 inhibitor, NS398. Subsequently, the cells were co-cultured with Jurkat T cell leukemia cells and damage to Jurkat cells was determined. Treatment with NS398 resulted in reduction of expression of FasL and TRAIL in HCA7 cells, whereas NS398 did not affect the expression of FasL and TRAIL in HCT116 cells. The number of viable Jurkat cells was diminished when cells were co-cultured with naive, non-pretreated HCA7 or HCA116 cells. Preincubation of HCA7 cells with NS398 before co-culture blunted the HCA7 cell-induced cell toxicity on Jurkat cells. In contrast, pretreatment with NS398 failed to inhibit the HCT116-induced Jurkat cell killing. Our results suggest that COX2 regulates the expression of FasL and TRAIL on COX2-positive colon cancer cells thereby evoking a counter-attack against cytotoxic T cells, which may lead to compromised host immune responses.

No MeSH data available.


Related in: MedlinePlus

Working hypothesis. For details, refer to the text.
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Figure 7: Working hypothesis. For details, refer to the text.

Mentions: Although the anti-cancer efficacy of COX2 selective inhibitors has been reported, most of studies have focused on the direct effects on tumorigenicity and/or malignant potentials of colon cancer cells [15–17, 34, 35]. Our results indicate that COX2 regulates the expression of FasL and TRAIL on COX2-positive colon cancer cells thereby evoking a counter-attack against CTLs leading to compromised host immune responses (Fig. 7). This adds to a new insight into the role of COX2 in the progression of colon cancer cells given that numerous numbers of immune cells are infiltrated in and adjacent to colon tumors [20], an event constituting a defense mechanism against tumors through damaging tumor cells. As COX2 is expressed at an early stage of colon neoplasm [7], the effects of COX2 inhibitors on preventing the counterattack potentials of tumor cells through reduction of FasL and TRAIL may explain, at least in part, a mechanism for the chemopreventive effects of COX2 selective inhibitors.


Cyclooxygenase 2 modulates killing of cytotoxic T lymphocytes by colon cancer cells.

Wang Q, Takei Y, Kobayashi O, Osada T, Watanabe S - J Clin Biochem Nutr (2009)

Working hypothesis. For details, refer to the text.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2735628&req=5

Figure 7: Working hypothesis. For details, refer to the text.
Mentions: Although the anti-cancer efficacy of COX2 selective inhibitors has been reported, most of studies have focused on the direct effects on tumorigenicity and/or malignant potentials of colon cancer cells [15–17, 34, 35]. Our results indicate that COX2 regulates the expression of FasL and TRAIL on COX2-positive colon cancer cells thereby evoking a counter-attack against CTLs leading to compromised host immune responses (Fig. 7). This adds to a new insight into the role of COX2 in the progression of colon cancer cells given that numerous numbers of immune cells are infiltrated in and adjacent to colon tumors [20], an event constituting a defense mechanism against tumors through damaging tumor cells. As COX2 is expressed at an early stage of colon neoplasm [7], the effects of COX2 inhibitors on preventing the counterattack potentials of tumor cells through reduction of FasL and TRAIL may explain, at least in part, a mechanism for the chemopreventive effects of COX2 selective inhibitors.

Bottom Line: Treatment with NS398 resulted in reduction of expression of FasL and TRAIL in HCA7 cells, whereas NS398 did not affect the expression of FasL and TRAIL in HCT116 cells.The number of viable Jurkat cells was diminished when cells were co-cultured with naive, non-pretreated HCA7 or HCA116 cells.In contrast, pretreatment with NS398 failed to inhibit the HCT116-induced Jurkat cell killing.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.

ABSTRACT
Although anti-cancer effects of cyclooxygenase 2 (COX2) inhibitors have been reported, most studies focused on the direct effects of COX2 inhibiters on colon cancer cells. On the other hand, several types of cancers express Fas ligand (FasL) and/or TRAIL and mediate apoptosis of T cells in vitro. The "counter-attack" machinery may account for the mechanisms by which tumors evade host immune surveillance. In this study we determined if COX2 inhibitor could modulate effector molecules of cell death on colon cancer cells changing their effects on cytotoxic T lymphocytes. Colon adenocarcinoma cells, HCA7 and HCT116, the former COX2-positive and the latter COX2-negative, were pre-incubated with/without a COX2 inhibitor, NS398. Subsequently, the cells were co-cultured with Jurkat T cell leukemia cells and damage to Jurkat cells was determined. Treatment with NS398 resulted in reduction of expression of FasL and TRAIL in HCA7 cells, whereas NS398 did not affect the expression of FasL and TRAIL in HCT116 cells. The number of viable Jurkat cells was diminished when cells were co-cultured with naive, non-pretreated HCA7 or HCA116 cells. Preincubation of HCA7 cells with NS398 before co-culture blunted the HCA7 cell-induced cell toxicity on Jurkat cells. In contrast, pretreatment with NS398 failed to inhibit the HCT116-induced Jurkat cell killing. Our results suggest that COX2 regulates the expression of FasL and TRAIL on COX2-positive colon cancer cells thereby evoking a counter-attack against cytotoxic T cells, which may lead to compromised host immune responses.

No MeSH data available.


Related in: MedlinePlus