Inhibition of Osteopontin Reduces Liver Metastasis of Human Pancreatic Cancer Xenografts Injected into the Spleen in a Mouse Model

Overview

Journal Surg Today

Specialty General Surgery

Date 2010 Mar 27

PMID 20339989

Citations 4

Authors

Keisuke Ohno

Hidefumi Nishimori

Takahiro Yasoshima

Kenjiro Kamiguchi

Fumitake Hata

Rika Fukui

Koichi Okuya

Yasutoshi Kimura

Ryuichi Denno

Shigeyuki Kon

Toshimitsu Uede

Noriyuki Sato

Koichi Hirata

Affiliations

Soon will be listed here.

Abstract

Purpose: Pancreatic cancer is associated with the poorest prognosis of any digestive cancer due to the high incidence of liver metastasis. This study evaluated the possibility that osteopontin (OPN) RNA interference (RNAi) and anti-OPN antibody (Ab) could have antimetastatic effects.

Methods: The differential gene expression was measured in a parental cell line, HPC-3, and an established highly liver metastatic cell line, HPC-3H4. This study investigated the effect of OPN RNAi and anti-OPN Ab on the metastatic ability of HPC-3H4 to the liver. An OPN RNAi-expressing vector was introduced into HPC-3H4 cells (HPC-3H4/miOPN), in which OPN production was reduced to the level of the parental HPC-3 cells. Finally, the ability of anti-OPN Ab to suppress liver metastasis was investigated.

Results: Osteopontin was upregulated 11.1-fold in HPC-3H4 in comparison to HPC-3. The metastatic rate of HPC-3H4/miOPN was significantly reduced to 25% in comparison to the 100% metastatic rate of HPC-3H4 and control HPC-3H4/miNeg cells (P < 0.01). The metastatic rate of the group given anti-OPN Ab was 50%.

Conclusion: OPN RNAi and anti-OPN Ab had remarkable inhibitory effects against liver metastasis by the pancreatic cancer cell line.

Citing Articles

The Role of Adipokines in Pancreatic Cancer.

Wang Q, Wang H, Ding Y, Wan M, Xu M Front Oncol. 2022; 12:926230.

PMID: 35875143 PMC: 9305334. DOI: 10.3389/fonc.2022.926230.

The role of osteopontin in the progression of solid organ tumour.

Zhao H, Chen Q, Alam A, Cui J, Suen K, Pac Soo A Cell Death Dis. 2018; 9(3):356.

PMID: 29500465 PMC: 5834520. DOI: 10.1038/s41419-018-0391-6.

SIBLINGs and SPARC families: their emerging roles in pancreatic cancer.

Kaleagasioglu F, Berger M World J Gastroenterol. 2014; 20(40):14747-59.

PMID: 25356037 PMC: 4209540. DOI: 10.3748/wjg.v20.i40.14747.

Aerosol delivery of small hairpin osteopontin blocks pulmonary metastasis of breast cancer in mice.

Yu K, Minai-Tehrani A, Chang S, Hwang S, Hong S, Kim J PLoS One. 2011; 5(12):e15623.

PMID: 21203518 PMC: 3008732. DOI: 10.1371/journal.pone.0015623.

References

Nishimori H, Yasoshima T, Hata F, Denno R, Yanai Y, Nomura H . A novel nude mouse model of liver metastasis and peritoneal dissemination from the same human pancreatic cancer line. Pancreas. 2002; 24(3):242-50. DOI: 10.1097/00006676-200204000-00006. View

Wu Y, Denhardt D, Rittling S . Osteopontin is required for full expression of the transformed phenotype by the ras oncogene. Br J Cancer. 2000; 83(2):156-63. PMC: 2363489. DOI: 10.1054/bjoc.2000.1200. View

Kim Y, Park Y, Lee J, Ko S, Yang M . Expression of osteopontin and osteonectin in breast cancer. J Korean Med Sci. 1999; 13(6):652-7. PMC: 3054552. DOI: 10.3346/jkms.1998.13.6.652. View

Ohno K, Hata F, Nishimori H, Yasoshima T, Yanai Y, Sogahata K . Metastatic-associated biological properties and differential gene expression profiles in established highly liver and peritoneal metastatic cell lines of human pancreatic cancer. J Exp Clin Cancer Res. 2004; 22(4):623-31. View

Tuck A, Hota C, Chambers A . Osteopontin(OPN)-induced increase in human mammary epithelial cell invasiveness is urokinase (uPA)-dependent. Breast Cancer Res Treat. 2002; 70(3):197-204. DOI: 10.1023/a:1013095329825. View

Behrend E, Craig A, Wilson S, Denhardt D, Chambers A . Reduced malignancy of ras-transformed NIH 3T3 cells expressing antisense osteopontin RNA. Cancer Res. 1994; 54(3):832-7. View

Kim J, Skates S, Uede T, Wong K, Schorge J, Feltmate C . Osteopontin as a potential diagnostic biomarker for ovarian cancer. JAMA. 2002; 287(13):1671-9. DOI: 10.1001/jama.287.13.1671. View

Bayless K, Davis G . Identification of dual alpha 4beta1 integrin binding sites within a 38 amino acid domain in the N-terminal thrombin fragment of human osteopontin. J Biol Chem. 2001; 276(16):13483-9. DOI: 10.1074/jbc.M011392200. View

Yamaguchi K, Ura H, Yasoshima T, Shishido T, Denno R, Hirata K . Establishment and characterization of a human gastric carcinoma cell line that is highly metastatic to lymph nodes. J Exp Clin Cancer Res. 2000; 19(1):113-20. View

10.

Rudland P, Platt-Higgins A, El-Tanani M, de Silva Rudland S, Barraclough R, Winstanley J . Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer. Cancer Res. 2002; 62(12):3417-27. View

11.

Ye Q, Qin L, Forgues M, He P, Kim J, Peng A . Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nat Med. 2003; 9(4):416-23. DOI: 10.1038/nm843. View

12.

Shishido T, Yasoshima T, Hirata K, Denno R, Mukaiya M, Ura H . Establishment and characterization of human pancreatic carcinoma lines with a high metastatic potential in the liver of nude mice. Surg Today. 1999; 29(6):519-25. DOI: 10.1007/BF02482346. View

13.

Oates A, Barraclough R, Rudland P . The identification of osteopontin as a metastasis-related gene product in a rodent mammary tumour model. Oncogene. 1996; 13(1):97-104. View

14.

Agrawal D, Chen T, Irby R, Quackenbush J, Chambers A, Szabo M . Osteopontin identified as lead marker of colon cancer progression, using pooled sample expression profiling. J Natl Cancer Inst. 2002; 94(7):513-21. DOI: 10.1093/jnci/94.7.513. View

15.

OBrien E, Garvin M, STEWART D, Hinohara T, Simpson J, Schwartz S . Osteopontin is synthesized by macrophage, smooth muscle, and endothelial cells in primary and restenotic human coronary atherosclerotic plaques. Arterioscler Thromb. 1994; 14(10):1648-56. DOI: 10.1161/01.atv.14.10.1648. View

16.

Yamamoto N, Sakai F, Kon S, Morimoto J, Kimura C, Yamazaki H . Essential role of the cryptic epitope SLAYGLR within osteopontin in a murine model of rheumatoid arthritis. J Clin Invest. 2003; 112(2):181-8. PMC: 164290. DOI: 10.1172/JCI17778. View

17.

Nomura H, Nishimori H, Yasoshima T, Hata F, Tanaka H, Nakajima F . A new liver metastatic and peritoneal dissemination model established from the same human pancreatic cancer cell line: analysis using cDNA macroarray. Clin Exp Metastasis. 2002; 19(5):391-9. DOI: 10.1023/a:1016370532618. View

18.

Thalmann G, Sikes R, Devoll R, Kiefer J, Markwalder R, Klima I . Osteopontin: possible role in prostate cancer progression. Clin Cancer Res. 1999; 5(8):2271-7. View

19.

Weber G, Ashkar S, Glimcher M, CANTOR H . Receptor-ligand interaction between CD44 and osteopontin (Eta-1). Science. 1996; 271(5248):509-12. DOI: 10.1126/science.271.5248.509. View

20.

Nomura H, Nishimori H, Yasoshima T, Hata F, Sogahata K, Tanaka H . A novel experimental mouse model of peritoneal dissemination of human gastric cancer cells: analysis of the mechanism of peritoneal dissemination using cDNA macroarrays. Jpn J Cancer Res. 2001; 92(7):748-54. PMC: 5926777. DOI: 10.1111/j.1349-7006.2001.tb01157.x. View