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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

Proliferation and apoptosis analyses of effects of neutrophils on oncogenic hepatocytes. 8 dpf fabp10+ and kras+ larvae after exposure to FPR A14 or PR-39 with doxycycline were analysed by immunohistochemistry. (A and C) PCNA (A) or active caspase 3 (B) staining with representative images from each group. Control Fabp10+ larvae with DsRed expression in hepatocytes were stained with Alexa Fluor 488-conjugated secondary antibody after the primary antibody incubation (top rows) while kras+ larvae with GFP expression in hepatocytes were stained with Alexa Fluor 568-conjugated secondary antibody (bottom rows). All sections were counter-stained with DAPI. (B and D) Quantification of proliferating (B) and apoptotic (D) hepatocytes as percentage of total hepatocytes (n = 10; *p <0.05; n.s., no significance).
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f0025: Proliferation and apoptosis analyses of effects of neutrophils on oncogenic hepatocytes. 8 dpf fabp10+ and kras+ larvae after exposure to FPR A14 or PR-39 with doxycycline were analysed by immunohistochemistry. (A and C) PCNA (A) or active caspase 3 (B) staining with representative images from each group. Control Fabp10+ larvae with DsRed expression in hepatocytes were stained with Alexa Fluor 488-conjugated secondary antibody after the primary antibody incubation (top rows) while kras+ larvae with GFP expression in hepatocytes were stained with Alexa Fluor 568-conjugated secondary antibody (bottom rows). All sections were counter-stained with DAPI. (B and D) Quantification of proliferating (B) and apoptotic (D) hepatocytes as percentage of total hepatocytes (n = 10; *p <0.05; n.s., no significance).

Mentions: To identify the causative factors for liver size change when neutrophil activity was modulated, hepatocyte proliferation and apoptosis were examined. As shown in Fig. 5, there were significant increases of hepatocyte proliferation and apoptosis in doxycycline-induced kras+ larvae, suggesting highly aberrant cell division and death in oncogenic livers. While co-exposure to FPR-A14/doxycycline did not induce a further increase of proliferating hepatocytes, it did lead to a significant reduction of apoptotic hepatocytes. In contrast, co-treatment of kras+ larvae with PR-39/doxycycline reduced the number of proliferating hepatocytes and increased the number of apoptotic hepatocytes. Thus, the changes in neutrophil activity affect both proliferation and apoptosis of hepatocytes.


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)

Proliferation and apoptosis analyses of effects of neutrophils on oncogenic hepatocytes. 8 dpf fabp10+ and kras+ larvae after exposure to FPR A14 or PR-39 with doxycycline were analysed by immunohistochemistry. (A and C) PCNA (A) or active caspase 3 (B) staining with representative images from each group. Control Fabp10+ larvae with DsRed expression in hepatocytes were stained with Alexa Fluor 488-conjugated secondary antibody after the primary antibody incubation (top rows) while kras+ larvae with GFP expression in hepatocytes were stained with Alexa Fluor 568-conjugated secondary antibody (bottom rows). All sections were counter-stained with DAPI. (B and D) Quantification of proliferating (B) and apoptotic (D) hepatocytes as percentage of total hepatocytes (n = 10; *p <0.05; n.s., no significance).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4508360&req=5

f0025: Proliferation and apoptosis analyses of effects of neutrophils on oncogenic hepatocytes. 8 dpf fabp10+ and kras+ larvae after exposure to FPR A14 or PR-39 with doxycycline were analysed by immunohistochemistry. (A and C) PCNA (A) or active caspase 3 (B) staining with representative images from each group. Control Fabp10+ larvae with DsRed expression in hepatocytes were stained with Alexa Fluor 488-conjugated secondary antibody after the primary antibody incubation (top rows) while kras+ larvae with GFP expression in hepatocytes were stained with Alexa Fluor 568-conjugated secondary antibody (bottom rows). All sections were counter-stained with DAPI. (B and D) Quantification of proliferating (B) and apoptotic (D) hepatocytes as percentage of total hepatocytes (n = 10; *p <0.05; n.s., no significance).
Mentions: To identify the causative factors for liver size change when neutrophil activity was modulated, hepatocyte proliferation and apoptosis were examined. As shown in Fig. 5, there were significant increases of hepatocyte proliferation and apoptosis in doxycycline-induced kras+ larvae, suggesting highly aberrant cell division and death in oncogenic livers. While co-exposure to FPR-A14/doxycycline did not induce a further increase of proliferating hepatocytes, it did lead to a significant reduction of apoptotic hepatocytes. In contrast, co-treatment of kras+ larvae with PR-39/doxycycline reduced the number of proliferating hepatocytes and increased the number of apoptotic hepatocytes. Thus, the changes in neutrophil activity affect both proliferation and apoptosis of hepatocytes.

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