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B7-H3 overexpression in pancreatic cancer promotes tumor progression.

Zhao X, Li DC, Zhu XG, Gan WJ, Li Z, Xiong F, Zhang ZX, Zhang GB, Zhang XG, Zhao H - Int. J. Mol. Med. (2012)

Bottom Line: In the present study, we compared B7-H3 expression in normal pancreas and pancreatic cancer tissue specimens, and determined the effects of low B7-H3 expression on the human pancreatic cancer cell line Patu8988 using lentivirus-mediated RNA interference.This demonstrated that inhibition of B7-H3 expression reduced pancreatic cancer metastasis in vivo.In conclusion, B7-H3 is aberrantly expressed in pancreatic cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, P.R. China.

ABSTRACT
B7-H3, a member of the B7-family molecules, plays an important role in adaptive immune responses. In addition, B7-H3 is also expressed in several types of human cancers and is correlated with the poor outcome of cancer patients. However, its exact role in cancer is not known. In the present study, we compared B7-H3 expression in normal pancreas and pancreatic cancer tissue specimens, and determined the effects of low B7-H3 expression on the human pancreatic cancer cell line Patu8988 using lentivirus-mediated RNA interference. B7-H3 expression in pancreatic specimens was determined by enzyme-linked immunosorbent assay (ELISA). A Patu8988 cell line with low B7-H3 expression was established by lentivirus-mediated RNA interference to investigate the effect of B7-H3 on cell proliferation, migration and invasion in vitro. By establishing subcutaneous transplantation tumor and orthotopic transplantation pancreatic cancer mouse models, the effect of B7-H3 on cell proliferation, migration and invasion was studied in vivo. B7-H3 in tissue samples was significantly higher in the pancreatic cancer group than in the normal pancreas group (mean ± SD, 193.6±9.352 vs. 87.74±7.433 ng/g; P<0.0001). B7-H3 knockdown by RNA interference decreased cell migration and Transwell invasion up to 50% in vitro. No apparent impact was observed on cell proliferation in vitro. In the subcutaneous transplantation tumor mouse model, the tumor growth rate was reduced by the knockdown of B7-H3. In the orthotopic transplantation pancreatic cancer mouse model, the effect of inhibiting metastasis by knocking down B7-H3 was assessed in terms of the average postmortem abdominal visceral metastatic tumor weight. This demonstrated that inhibition of B7-H3 expression reduced pancreatic cancer metastasis in vivo. In conclusion, B7-H3 is aberrantly expressed in pancreatic cancer. In addition to modulating tumor immunity, B7-H3 may have a novel role in regulating pancreatic tumor progression.

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Efficiency of infection as detected by GFP expression using fluorescence microscopy.Patu8988 cells were infected with lentivirus LV-B7-H3 and lentivirus LV-NC,respectively. Phase contrast and GFP expression were assessed under a fluorescencemicroscope. (Magnification, ×200).
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f3-ijmm-31-02-0283: Efficiency of infection as detected by GFP expression using fluorescence microscopy.Patu8988 cells were infected with lentivirus LV-B7-H3 and lentivirus LV-NC,respectively. Phase contrast and GFP expression were assessed under a fluorescencemicroscope. (Magnification, ×200).

Mentions: After infection with the lentiviral vector, Patu8988 cells were examined by fluorescencemicroscopy (Fig. 3). The resultshowed high efficiency of the lentiviral infection. To determine the efficiency of RNAinterference, we analyzed the levels of B7-H3 mRNA and protein expression in the 3 groups.Fig. 4A and B shows B7-H3 mRNAexpression in the 3 groups. B7-H3 mRNA expression was obviously decreased in the LV-B7-H3group compared with the LV-NC or the control groups (mean 8.4±2.15%,P<0.01) (Fig. 4B). Theinhibition rate was 91.6%. However, there was no significant difference betweenthe LV-NC group and the control group (P>0.05). A similar decrease was found inprotein synthesis by FCM assay (mean 20.6±5.9%, P<0.01) (Fig. 4C). The mean inhibition rate was79.4% vs. the control group. These findings indicate that the downregulation ofthe B7-H3 gene, by RNA interference was specific and efficient.


B7-H3 overexpression in pancreatic cancer promotes tumor progression.

Zhao X, Li DC, Zhu XG, Gan WJ, Li Z, Xiong F, Zhang ZX, Zhang GB, Zhang XG, Zhao H - Int. J. Mol. Med. (2012)

Efficiency of infection as detected by GFP expression using fluorescence microscopy.Patu8988 cells were infected with lentivirus LV-B7-H3 and lentivirus LV-NC,respectively. Phase contrast and GFP expression were assessed under a fluorescencemicroscope. (Magnification, ×200).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4042878&req=5

f3-ijmm-31-02-0283: Efficiency of infection as detected by GFP expression using fluorescence microscopy.Patu8988 cells were infected with lentivirus LV-B7-H3 and lentivirus LV-NC,respectively. Phase contrast and GFP expression were assessed under a fluorescencemicroscope. (Magnification, ×200).
Mentions: After infection with the lentiviral vector, Patu8988 cells were examined by fluorescencemicroscopy (Fig. 3). The resultshowed high efficiency of the lentiviral infection. To determine the efficiency of RNAinterference, we analyzed the levels of B7-H3 mRNA and protein expression in the 3 groups.Fig. 4A and B shows B7-H3 mRNAexpression in the 3 groups. B7-H3 mRNA expression was obviously decreased in the LV-B7-H3group compared with the LV-NC or the control groups (mean 8.4±2.15%,P<0.01) (Fig. 4B). Theinhibition rate was 91.6%. However, there was no significant difference betweenthe LV-NC group and the control group (P>0.05). A similar decrease was found inprotein synthesis by FCM assay (mean 20.6±5.9%, P<0.01) (Fig. 4C). The mean inhibition rate was79.4% vs. the control group. These findings indicate that the downregulation ofthe B7-H3 gene, by RNA interference was specific and efficient.

Bottom Line: In the present study, we compared B7-H3 expression in normal pancreas and pancreatic cancer tissue specimens, and determined the effects of low B7-H3 expression on the human pancreatic cancer cell line Patu8988 using lentivirus-mediated RNA interference.This demonstrated that inhibition of B7-H3 expression reduced pancreatic cancer metastasis in vivo.In conclusion, B7-H3 is aberrantly expressed in pancreatic cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, P.R. China.

ABSTRACT
B7-H3, a member of the B7-family molecules, plays an important role in adaptive immune responses. In addition, B7-H3 is also expressed in several types of human cancers and is correlated with the poor outcome of cancer patients. However, its exact role in cancer is not known. In the present study, we compared B7-H3 expression in normal pancreas and pancreatic cancer tissue specimens, and determined the effects of low B7-H3 expression on the human pancreatic cancer cell line Patu8988 using lentivirus-mediated RNA interference. B7-H3 expression in pancreatic specimens was determined by enzyme-linked immunosorbent assay (ELISA). A Patu8988 cell line with low B7-H3 expression was established by lentivirus-mediated RNA interference to investigate the effect of B7-H3 on cell proliferation, migration and invasion in vitro. By establishing subcutaneous transplantation tumor and orthotopic transplantation pancreatic cancer mouse models, the effect of B7-H3 on cell proliferation, migration and invasion was studied in vivo. B7-H3 in tissue samples was significantly higher in the pancreatic cancer group than in the normal pancreas group (mean ± SD, 193.6±9.352 vs. 87.74±7.433 ng/g; P<0.0001). B7-H3 knockdown by RNA interference decreased cell migration and Transwell invasion up to 50% in vitro. No apparent impact was observed on cell proliferation in vitro. In the subcutaneous transplantation tumor mouse model, the tumor growth rate was reduced by the knockdown of B7-H3. In the orthotopic transplantation pancreatic cancer mouse model, the effect of inhibiting metastasis by knocking down B7-H3 was assessed in terms of the average postmortem abdominal visceral metastatic tumor weight. This demonstrated that inhibition of B7-H3 expression reduced pancreatic cancer metastasis in vivo. In conclusion, B7-H3 is aberrantly expressed in pancreatic cancer. In addition to modulating tumor immunity, B7-H3 may have a novel role in regulating pancreatic tumor progression.

Show MeSH
Related in: MedlinePlus