Limits...
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.

Show MeSH

Related in: MedlinePlus

Metastatic tumors in the orthotopic transplantation pancreatic cancer mouse model. (A)An orthotopic transplantation pancreatic cancer mouse model was established. Orthotopicpancreatic cancer tumors, liver metastatic tumors and abdominal cavity metastatic tumorsare indicated by red, white and blue arrows, respectively. (B) Seven weeks after theorthotopic transplantation operation, metastatic visceral tumors out of the pancreaswere excised and weighed. Each group consisted of 6 animals, and the data are presentedas means ± SD. The tumor weight of the LV-B7-H3 group was obviously lower whencompared with the LV-NC and control group (*P<0.01 vs. thecontrol group).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4042878&req=5

f10-ijmm-31-02-0283: Metastatic tumors in the orthotopic transplantation pancreatic cancer mouse model. (A)An orthotopic transplantation pancreatic cancer mouse model was established. Orthotopicpancreatic cancer tumors, liver metastatic tumors and abdominal cavity metastatic tumorsare indicated by red, white and blue arrows, respectively. (B) Seven weeks after theorthotopic transplantation operation, metastatic visceral tumors out of the pancreaswere excised and weighed. Each group consisted of 6 animals, and the data are presentedas means ± SD. The tumor weight of the LV-B7-H3 group was obviously lower whencompared with the LV-NC and control group (*P<0.01 vs. thecontrol group).

Mentions: All of the 18 mice were sacrificed 7 weeks after the transplantation operation. All ofthe mice developed orthotopic transplantation pancreatic cancer tumors in this experiment.Abdominal visceral metastatic tumors were detected, excised and weighed (Fig. 10). The number of cases of livermetastasis in the LV-B7-H3 group (1/6, 16.67%) was less than the number of casesin the LV-NC group (4/6, 66.67%) or the control group (5/6, 83.33%). Theeffect of inhibiting metastasis by knockdown of B7-H3 was assessed in terms of the averagepostmortem abdominal visceral metastatic tumor weight. Inhibition of metastasis wasobserved in the LV-B7-H3 group, when compared to the LV-NC group (1.28±0.41 g) orthe control group (1.33±0.38 g). The average weight of the abdominal visceralmetastatic tumors (0.26±0.13 g) in the LV-B7-H3 group was significantly lower thanthat in LV-NC and control groups (Fig.10B) (P<0.01). There was no statistical significance in metastaticvisceral tumor weight between the LV-NC and the control group (P>0.05). Theseindicated that inhibition of B7-H3 expression reduced pancreatic cancer metastasisin vivo. It strongly supports the effects observed invitro indicating that B7-H3 plays a vital role in invasion and migration ofpancreatic cancer cells.


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)

Metastatic tumors in the orthotopic transplantation pancreatic cancer mouse model. (A)An orthotopic transplantation pancreatic cancer mouse model was established. Orthotopicpancreatic cancer tumors, liver metastatic tumors and abdominal cavity metastatic tumorsare indicated by red, white and blue arrows, respectively. (B) Seven weeks after theorthotopic transplantation operation, metastatic visceral tumors out of the pancreaswere excised and weighed. Each group consisted of 6 animals, and the data are presentedas means ± SD. The tumor weight of the LV-B7-H3 group was obviously lower whencompared with the LV-NC and control group (*P<0.01 vs. thecontrol group).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f10-ijmm-31-02-0283: Metastatic tumors in the orthotopic transplantation pancreatic cancer mouse model. (A)An orthotopic transplantation pancreatic cancer mouse model was established. Orthotopicpancreatic cancer tumors, liver metastatic tumors and abdominal cavity metastatic tumorsare indicated by red, white and blue arrows, respectively. (B) Seven weeks after theorthotopic transplantation operation, metastatic visceral tumors out of the pancreaswere excised and weighed. Each group consisted of 6 animals, and the data are presentedas means ± SD. The tumor weight of the LV-B7-H3 group was obviously lower whencompared with the LV-NC and control group (*P<0.01 vs. thecontrol group).
Mentions: All of the 18 mice were sacrificed 7 weeks after the transplantation operation. All ofthe mice developed orthotopic transplantation pancreatic cancer tumors in this experiment.Abdominal visceral metastatic tumors were detected, excised and weighed (Fig. 10). The number of cases of livermetastasis in the LV-B7-H3 group (1/6, 16.67%) was less than the number of casesin the LV-NC group (4/6, 66.67%) or the control group (5/6, 83.33%). Theeffect of inhibiting metastasis by knockdown of B7-H3 was assessed in terms of the averagepostmortem abdominal visceral metastatic tumor weight. Inhibition of metastasis wasobserved in the LV-B7-H3 group, when compared to the LV-NC group (1.28±0.41 g) orthe control group (1.33±0.38 g). The average weight of the abdominal visceralmetastatic tumors (0.26±0.13 g) in the LV-B7-H3 group was significantly lower thanthat in LV-NC and control groups (Fig.10B) (P<0.01). There was no statistical significance in metastaticvisceral tumor weight between the LV-NC and the control group (P>0.05). Theseindicated that inhibition of B7-H3 expression reduced pancreatic cancer metastasisin vivo. It strongly supports the effects observed invitro indicating that B7-H3 plays a vital role in invasion and migration ofpancreatic cancer cells.

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