Inhibition of osteopontin reduces liver metastasis of human pancreatic cancer xenografts injected into the spleen in a mouse model

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 diff...

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Veröffentlicht in:Surgery today (Tokyo, Japan) Japan), 2010-04, Vol.40 (4), p.347-356
Hauptverfasser: Ohno, Keisuke, Nishimori, Hidefumi, Yasoshima, Takahiro, Kamiguchi, Kenjiro, Hata, Fumitake, Fukui, Rika, Okuya, Koichi, Kimura, Yasutoshi, Denno, Ryuichi, Kon, Shigeyuki, Uede, Toshimitsu, Sato, Noriyuki, Hirata, Koichi
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container_end_page 356
container_issue 4
container_start_page 347
container_title Surgery today (Tokyo, Japan)
container_volume 40
creator Ohno, Keisuke
Nishimori, Hidefumi
Yasoshima, Takahiro
Kamiguchi, Kenjiro
Hata, Fumitake
Fukui, Rika
Okuya, Koichi
Kimura, Yasutoshi
Denno, Ryuichi
Kon, Shigeyuki
Uede, Toshimitsu
Sato, Noriyuki
Hirata, Koichi
description 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.
doi_str_mv 10.1007/s00595-009-4082-x
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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 &lt; 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.</description><identifier>ISSN: 0941-1291</identifier><identifier>EISSN: 1436-2813</identifier><identifier>DOI: 10.1007/s00595-009-4082-x</identifier><identifier>PMID: 20339989</identifier><language>eng</language><publisher>Japan: Springer Japan</publisher><subject>Animals ; Antibodies - pharmacology ; Cell Line, Tumor ; Enzyme-Linked Immunosorbent Assay ; Female ; Gene Expression ; Genetic Vectors ; Humans ; Liver Neoplasms - prevention &amp; control ; Liver Neoplasms - secondary ; Medicine ; Medicine &amp; Public Health ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microarray Analysis ; Original Article ; Osteopontin - genetics ; Osteopontin - immunology ; Osteopontin - physiology ; Pancreatic Neoplasms - pathology ; Reverse Transcriptase Polymerase Chain Reaction ; RNA ; RNA Interference ; Surgery ; Surgical Oncology ; Transfection ; Transplantation, Heterologous</subject><ispartof>Surgery today (Tokyo, Japan), 2010-04, Vol.40 (4), p.347-356</ispartof><rights>Springer 2010</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-2d42352aa3390ed01998491ead314ee0f1dded8a198de40a9aa8c64720a41683</citedby><cites>FETCH-LOGICAL-c396t-2d42352aa3390ed01998491ead314ee0f1dded8a198de40a9aa8c64720a41683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00595-009-4082-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00595-009-4082-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20339989$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ohno, Keisuke</creatorcontrib><creatorcontrib>Nishimori, Hidefumi</creatorcontrib><creatorcontrib>Yasoshima, Takahiro</creatorcontrib><creatorcontrib>Kamiguchi, Kenjiro</creatorcontrib><creatorcontrib>Hata, Fumitake</creatorcontrib><creatorcontrib>Fukui, Rika</creatorcontrib><creatorcontrib>Okuya, Koichi</creatorcontrib><creatorcontrib>Kimura, Yasutoshi</creatorcontrib><creatorcontrib>Denno, Ryuichi</creatorcontrib><creatorcontrib>Kon, Shigeyuki</creatorcontrib><creatorcontrib>Uede, Toshimitsu</creatorcontrib><creatorcontrib>Sato, Noriyuki</creatorcontrib><creatorcontrib>Hirata, Koichi</creatorcontrib><title>Inhibition of osteopontin reduces liver metastasis of human pancreatic cancer xenografts injected into the spleen in a mouse model</title><title>Surgery today (Tokyo, Japan)</title><addtitle>Surg Today</addtitle><addtitle>Surg Today</addtitle><description>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 &lt; 0.01). The metastatic rate of the group given anti-OPN Ab was 50%. 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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 &lt; 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.</abstract><cop>Japan</cop><pub>Springer Japan</pub><pmid>20339989</pmid><doi>10.1007/s00595-009-4082-x</doi><tpages>10</tpages></addata></record>
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ispartof Surgery today (Tokyo, Japan), 2010-04, Vol.40 (4), p.347-356
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1436-2813
language eng
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subjects Animals
Antibodies - pharmacology
Cell Line, Tumor
Enzyme-Linked Immunosorbent Assay
Female
Gene Expression
Genetic Vectors
Humans
Liver Neoplasms - prevention & control
Liver Neoplasms - secondary
Medicine
Medicine & Public Health
Mice
Mice, Inbred BALB C
Mice, Nude
Microarray Analysis
Original Article
Osteopontin - genetics
Osteopontin - immunology
Osteopontin - physiology
Pancreatic Neoplasms - pathology
Reverse Transcriptase Polymerase Chain Reaction
RNA
RNA Interference
Surgery
Surgical Oncology
Transfection
Transplantation, Heterologous
title Inhibition of osteopontin reduces liver metastasis of human pancreatic cancer xenografts injected into the spleen in a mouse model
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