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Stimulation of hepatocarcinogenesis by neutrophils upon induction of oncogenic kras expression in transgenic zebrafish.

Yan C, Huo X, Wang S, Feng Y, Gong Z - J. Hepatol. (2015)

Bottom Line: Both oncogenic hepatocytes and tumor-associated neutrophils (TANs) were isolated via fluorescence-activated cell sorting.Molecular analyses indicated a pro-inflammatory microenvironment, as marked by increased tgfβ1a expression in kras(V12)-expressing hepatocytes and a loss of anti-tumor activities in TANs.Depletion of Tgf-β significantly reduced the number of TANs and the size of oncogenic liver.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, National University of Singapore, Singapore; National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.

No MeSH data available.


Related in: MedlinePlus

Differential behaviors of NNs and TANs. (A–B) Tracking of neutrophil movement within and surrounding the liver area in a kras−/lyz+ larva (A) and a kras+/lyz+ larva (B) respectively. Selected neutrophils were tracked based on one-hour time-lapse videos on 8 dpf larvae in Supplementary Videos 1 and 2. (C) Representative images of three distinct nuclear patterns after Giemsa staining: circular, bi-lobed and segmented nuclei. (D) Percentages of each nuclear pattern in NNs and TANs.
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f0020: Differential behaviors of NNs and TANs. (A–B) Tracking of neutrophil movement within and surrounding the liver area in a kras−/lyz+ larva (A) and a kras+/lyz+ larva (B) respectively. Selected neutrophils were tracked based on one-hour time-lapse videos on 8 dpf larvae in Supplementary Videos 1 and 2. (C) Representative images of three distinct nuclear patterns after Giemsa staining: circular, bi-lobed and segmented nuclei. (D) Percentages of each nuclear pattern in NNs and TANs.

Mentions: Neutrophil migratory pattern was also examined using confocal time-lapse video and resulting in an obvious difference in neutrophil movement between kras+ and kras− larvae in the presence of doxycycline. In a 1-hour time-lapse video of 8 dpf kras+ larvae (Supplementary Video 1), neutrophils had active migratory movement surrounding the liver. However, within the liver, infiltrated neutrophils were rather stationary with only minimal movement. In kras− siblings (Supplementary Video 2), in contrast, neutrophils were uniformly active both within and outside the liver. The difference was further illustrated by tracking neutrophil movement from these videos using the Imaris software (Fig. 4A and B). Thus, the tumor microenvironment leads to an inactive migratory behavior of infiltrated neutrophils.


Stimulation of hepatocarcinogenesis by neutrophils upon induction of oncogenic kras expression in transgenic zebrafish.

Yan C, Huo X, Wang S, Feng Y, Gong Z - J. Hepatol. (2015)

Differential behaviors of NNs and TANs. (A–B) Tracking of neutrophil movement within and surrounding the liver area in a kras−/lyz+ larva (A) and a kras+/lyz+ larva (B) respectively. Selected neutrophils were tracked based on one-hour time-lapse videos on 8 dpf larvae in Supplementary Videos 1 and 2. (C) Representative images of three distinct nuclear patterns after Giemsa staining: circular, bi-lobed and segmented nuclei. (D) Percentages of each nuclear pattern in NNs and TANs.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4508360&req=5

f0020: Differential behaviors of NNs and TANs. (A–B) Tracking of neutrophil movement within and surrounding the liver area in a kras−/lyz+ larva (A) and a kras+/lyz+ larva (B) respectively. Selected neutrophils were tracked based on one-hour time-lapse videos on 8 dpf larvae in Supplementary Videos 1 and 2. (C) Representative images of three distinct nuclear patterns after Giemsa staining: circular, bi-lobed and segmented nuclei. (D) Percentages of each nuclear pattern in NNs and TANs.
Mentions: Neutrophil migratory pattern was also examined using confocal time-lapse video and resulting in an obvious difference in neutrophil movement between kras+ and kras− larvae in the presence of doxycycline. In a 1-hour time-lapse video of 8 dpf kras+ larvae (Supplementary Video 1), neutrophils had active migratory movement surrounding the liver. However, within the liver, infiltrated neutrophils were rather stationary with only minimal movement. In kras− siblings (Supplementary Video 2), in contrast, neutrophils were uniformly active both within and outside the liver. The difference was further illustrated by tracking neutrophil movement from these videos using the Imaris software (Fig. 4A and B). Thus, the tumor microenvironment leads to an inactive migratory behavior of infiltrated neutrophils.

Bottom Line: Both oncogenic hepatocytes and tumor-associated neutrophils (TANs) were isolated via fluorescence-activated cell sorting.Molecular analyses indicated a pro-inflammatory microenvironment, as marked by increased tgfβ1a expression in kras(V12)-expressing hepatocytes and a loss of anti-tumor activities in TANs.Depletion of Tgf-β significantly reduced the number of TANs and the size of oncogenic liver.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, National University of Singapore, Singapore; National University of Singapore Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.

No MeSH data available.


Related in: MedlinePlus