The Modulation of B16BL6 Melanoma Metastasis Is Not Directly Mediated by Cytolytic Activity of Natural Killer Cells in Alcohol-Consuming Mice

Spitzer, Jessica H.; N????ez, Nomel?? P.; Meadows, Sarah; Gallucci, Randle M.; Blank, Sally E.; Meadows, Gary G.

doi:10.1097/00000374-200006000-00013

Cited by 3 publications

(4 citation statements)

References 31 publications

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“…Herein we found that the decreased numbers of NK cells in the LN are associated with increased metastasis of melanoma into the draining LN after subcutaneous inoculation into the hip region. This is in contrast to our previous findings that alcohol consumption inhibits metastasis to the lung [25,26] even when NK cells were depleted with anti-NK1.1 antibody [25] or when melanoma cells were inoculated into beige mice, which have compromised NK cell activity [27]. The exact mechanism underlying these regional differences is not known.…”

Section: Discussioncontrasting

confidence: 85%

Chronic alcohol consumption decreases the percentage and number of NK cells in the peripheral lymph nodes and exacerbates B16BL6 melanoma metastasis into the draining lymph nodes

Zhang

Zhu

Meadows

2011

Cellular Immunology

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NK cells in the lymph nodes play important roles in inhibiting tumor metastasis into draining lymph nodes. Previously, we reported that chronic alcohol consumption interferes with NK cell trafficking from the bone marrow to the spleen. Herein, we found that alcohol consumption decreases the numbers of NK cells in lymph nodes. Adoptive transfer experiments indicated that continued exposure of donor splenocytes to alcohol inhibits NK but not T cell trafficking to lymph nodes. Alcohol did not negatively affect CCR7 + and CXCR3 + NK cells, but decreased the percentage and number of CD62L + NK cells in the spleen, which are an important source of NK cell trafficking into the lymph nodes. These data suggest that modulation of the microenvironment associated with alcohol consumption impairs the trafficking of NK cells to lymph nodes. The decreased number of NK cells in the lymph nodes was associated with increased melanoma metastasis into the draining lymph nodes.

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Section: Discussioncontrasting

confidence: 85%

Chronic alcohol consumption decreases the percentage and number of NK cells in the peripheral lymph nodes and exacerbates B16BL6 melanoma metastasis into the draining lymph nodes

Zhang

Zhu

Meadows

2011

Cellular Immunology

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“…Studies using subcutaneously injected B16F10 cells have shown that ethanol diminishes the number of pulmonary nodules compared with the control [77], while injection into the lateral vein of the tail significantly increases the metastatic effect of the ethanol [78], which was also observed in our study. These apparently contradictory effects of ethanol have been discussed in several studies: for example, in vitro studies have described the stimulatory effects of ethanol on cell migration both in the case of B16F10 melanoma [77] and other cell lines, such as breast cancer T47D [80]; other studies have described its action on endothelial fibrinolysis [81] and the inhibitory effect on platelet aggregation [82], which may reduce pulmonary metastasis.…”

Section: Anti-invasive Effectssupporting

confidence: 88%

Beneficial Action of Citrus Flavonoids on Multiple Cancer-Related Biological Pathways

Ortuño¹,

Benavente-García

Castillo

et al. 2007

CCDT

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Attempts to control cancer involve a variety of means, including the use of suppressing, blocking and transforming agents. Suppressing agents prevent the formation of new cancers from pro-carcinogens, blocking agents prevent carcinogenic compounds from reaching critical initiation sites, while transformation agents act to facilitate the metabolism of carcinogenic components into less toxic materials or to prevent their biological actions. Flavonoids can act as all three types of agent. Epidemiological and animal studies suggest that flavonoids have a protective effect against cardiovascular diseases and some types of cancer. Although flavonoids have been studied for about 50 years, the cellular mechanisms involved in their biological action are still not completely understood. In recent years, experimental studies have provided growing evidence supporting the beneficial action of flavonoids on multiple cancer-related biological pathways (carcinogen bio-activation, cell-signaling, cell cycle regulation, angiogenesis and inflammation). Within the last decade, reports on flavonoid activity have largely associated with enzyme inhibition and anti-proliferative activity. Many of these studies have pointed to a structural-functional relationship, in that the antioxidant, enzyme-inhibition or antiproliferative activities of flavonoids are dependent on particular structural motifs. Our own studies have shown that structural factors would explain the antioxidant, antiproliferative and antimetastatic properties of some citrus flavonoids. In this paper we discuss the relation between each structural factor and the anticancer activity of Citrus flavonoids.

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“…Using a mouse model of chronic alcohol consumption that mimics intake in human alcoholics, we found that B16BL6 melanoma metastasis to the lung is greatly decreased between 42 and 94% [19–21]. Our previous findings [19, 21] and the results of others [24, 25] indicate that NK cell cytolytic activity is not the major mechanism underlying control of melanoma metastasis. Until now the mechanisms associated with this effect have not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…inoculation via the lateral tail vein [19, 20]. The effect of alcohol on B16BL6 melanoma metastasis is dose dependent [20] and independent of perforin and granzymes related NK cell cytolytic activity, as demonstrated in beige mice [21]. …”

Section: Introductionmentioning

confidence: 99%

IFN-γ is essential for the inhibition of B16BL6 melanoma lung metastasis in chronic alcohol drinking mice

Zhang

Zhu

McKinley

et al. 2011

Clin Exp Metastasis

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We previously found that chronic alcohol consumption (20% w/v in drinking water) that models the level consumed by human alcoholics, when administered to female C57BL/6 mice inhibits B16BL6 melanoma metastasis to the lung; however, the mechanism is not known. Chronic alcohol consumption increases IFN-γ producing NK, NKT, CD4+, and CD8+ T cells. To examine the impact of IFN-γ on metastasis, we inoculated B16BL6 melanoma cells i.v. into control and chronic alcohol drinking IFN-γ knockout (KO) mice. Knockout of the ifn-γ gene abrogated the anti-metastatic effects associated with alcohol consumption. We examined metastasis in common gamma-chain (γC) KO mice, which are deficient in NK, NKT and CD8+ T cells, and in Vα14Jα281−/− KO mice, which are deficient in invariant NKT (iNKT) cells, in order to assess the importance of specific IFN-γ producing cell types to this effect. We found that the antimetastatic effect of alcohol was still present in γC KO mice and also in γC KO mice depleted of Gr-1+ cells. Knockout of iNKT cells reduced the degree but not the antimetastatic effect associated with alcohol. These results indicate that the anti-metastatic effect induced by chronic alcohol consumption is IFN-γ dependent and that multiple IFN-γ producing cell types contribute to this effect.

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The Modulation of B16BL6 Melanoma Metastasis Is Not Directly Mediated by Cytolytic Activity of Natural Killer Cells in Alcohol-Consuming Mice

Abstract: These data suggest that the presence of the beige mutation diminishes the antimetastatic effect of alcohol consumption and that there is no interaction between alcohol consumption and NK-cell activity in the modulation of lung metastasis of B16BL6 melanoma cells.

Cited by 3 publications

References 31 publications

Chronic alcohol consumption decreases the percentage and number of NK cells in the peripheral lymph nodes and exacerbates B16BL6 melanoma metastasis into the draining lymph nodes

Chronic alcohol consumption decreases the percentage and number of NK cells in the peripheral lymph nodes and exacerbates B16BL6 melanoma metastasis into the draining lymph nodes

Beneficial Action of Citrus Flavonoids on Multiple Cancer-Related Biological Pathways

IFN-γ is essential for the inhibition of B16BL6 melanoma lung metastasis in chronic alcohol drinking mice

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