Limits...
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

Effect of morpholino suppression of neutrophil differentiation and morpholino-mediated expansion of neutrophil population on liver size. (A–C) Representative images of 6 dpf kras−/lyz+ and kras+/lyz+ larvae injected with different morpholinos: Mo-SC (A), Mo-gcsfr (B) or Mo-irf8 (C). (D–F) Neutrophil counts (D) and density (E) in the liver area and liver size (F) after morpholino injection. n >15 in each group. Statistical significant: *p <0.05.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4508360&req=5

f0015: Effect of morpholino suppression of neutrophil differentiation and morpholino-mediated expansion of neutrophil population on liver size. (A–C) Representative images of 6 dpf kras−/lyz+ and kras+/lyz+ larvae injected with different morpholinos: Mo-SC (A), Mo-gcsfr (B) or Mo-irf8 (C). (D–F) Neutrophil counts (D) and density (E) in the liver area and liver size (F) after morpholino injection. n >15 in each group. Statistical significant: *p <0.05.

Mentions: To further validate the effect of neutrophils on tumor growth, differentiation of myeloid derived precursor cells into neutrophils was blocked via morpholino knockdown of the gcsfr gene (MO_gcsfr). MO_gcsfr or control morpholino (MO_SC) were injected into lyz+ embryos at one-cell stage and injected embryos were monitored for DsRed+ neutrophils. As shown in Supplementary Fig. 1A and C, by 6 dpf, there was an overall decrease of circulating neutrophils in MO_gscfr injected larvae, compared to those in lyz+ larvae injected with MO_SC, consistent with the previous report that used the same set of morpholinos [29]. kras+/lyz+ and kras−/lyz+ zebrafish embryos were then injected with MO_gscfr and analysed at 6 dpf after doxycycline induction from 3 dpf. Similar to the observations with the PR-39 inhibitor, a significant decrease of neutrophil counts and density in the liver (Fig. 3D and E) as well as liver size (Fig. 3F) was observed, further confirming a promoting role of neutrophils in the initial stage of hepatocarcinogenesis.


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)

Effect of morpholino suppression of neutrophil differentiation and morpholino-mediated expansion of neutrophil population on liver size. (A–C) Representative images of 6 dpf kras−/lyz+ and kras+/lyz+ larvae injected with different morpholinos: Mo-SC (A), Mo-gcsfr (B) or Mo-irf8 (C). (D–F) Neutrophil counts (D) and density (E) in the liver area and liver size (F) after morpholino injection. n >15 in each group. Statistical significant: *p <0.05.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4508360&req=5

f0015: Effect of morpholino suppression of neutrophil differentiation and morpholino-mediated expansion of neutrophil population on liver size. (A–C) Representative images of 6 dpf kras−/lyz+ and kras+/lyz+ larvae injected with different morpholinos: Mo-SC (A), Mo-gcsfr (B) or Mo-irf8 (C). (D–F) Neutrophil counts (D) and density (E) in the liver area and liver size (F) after morpholino injection. n >15 in each group. Statistical significant: *p <0.05.
Mentions: To further validate the effect of neutrophils on tumor growth, differentiation of myeloid derived precursor cells into neutrophils was blocked via morpholino knockdown of the gcsfr gene (MO_gcsfr). MO_gcsfr or control morpholino (MO_SC) were injected into lyz+ embryos at one-cell stage and injected embryos were monitored for DsRed+ neutrophils. As shown in Supplementary Fig. 1A and C, by 6 dpf, there was an overall decrease of circulating neutrophils in MO_gscfr injected larvae, compared to those in lyz+ larvae injected with MO_SC, consistent with the previous report that used the same set of morpholinos [29]. kras+/lyz+ and kras−/lyz+ zebrafish embryos were then injected with MO_gscfr and analysed at 6 dpf after doxycycline induction from 3 dpf. Similar to the observations with the PR-39 inhibitor, a significant decrease of neutrophil counts and density in the liver (Fig. 3D and E) as well as liver size (Fig. 3F) was observed, further confirming a promoting role of neutrophils in the initial stage of hepatocarcinogenesis.

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