Identification of Keratin 19-Positive Cancer Stem Cells Associating Human Hepatocellular Carcinoma Using 18 F-Fluorodeoxyglucose Positron Emission Tomography
The current lack of tools for easy assessment of cancer stem cells (CSC) prevents the development of therapeutic strategies for hepatocellular carcinoma (HCC). We previously reported that keratin 19 (K19) is a novel HCC-CSC marker and that PET with F-fluorodeoxyglucose ( F-FDG) is an effective metho...
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| Veröffentlicht in: | Clinical cancer research 2017-03, Vol.23 (6), p.1450 |
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| creator | Kawai, Takayuki Yasuchika, Kentaro Seo, Satoru Higashi, Tatsuya Ishii, Takamichi Miyauchi, Yuya Kojima, Hidenobu Yamaoka, Ryoya Katayama, Hokahiro Yoshitoshi, Elena Yukie Ogiso, Satoshi Kita, Sadahiko Yasuda, Katsutaro Fukumitsu, Ken Nakamoto, Yuji Hatano, Etsuro Uemoto, Shinji |
| description | The current lack of tools for easy assessment of cancer stem cells (CSC) prevents the development of therapeutic strategies for hepatocellular carcinoma (HCC). We previously reported that keratin 19 (K19) is a novel HCC-CSC marker and that PET with
F-fluorodeoxyglucose (
F-FDG) is an effective method for predicting postoperative outcome in hepatocellular carcinoma. Herein, we examined whether K19
HCC-CSCs can be tracked using
F-FDG-PET.
K19 and glucose transporter-1 (GLUT1) expression was evaluated by IHC in 98 hepatocellular carcinoma patients who underwent
F-FDG-PET scans before primary tumor resection. Standardized uptake values (SUV) for primary tumors and tumor-to-nontumor SUV ratios (TNR) were calculated using FDG accumulation levels, and values were compared among K19
/K19
patients. Using hepatocellular carcinoma cell lines encoding with a K19 promoter-driven enhanced GFP,
F-FDG uptake and GLUT1 expression were examined in FACS-isolated K19
/K19
cells.
In hepatocellular carcinoma patients, K19 expression was significantly correlated with GLUT1 expression and FDG accumulation. ROC analyses revealed that among preoperative clinical factors, TNR was the most sensitive indicator of K19 expression in hepatocellular carcinoma tumors. In hepatocellular carcinoma cells, FACS-isolated K19
cells displayed significantly higher
F-FDG uptake than K19
cells. Moreover, gain/loss-of-function experiments confirmed that K19 regulates
F-FDG uptake through TGFβ/Smad signaling, including Sp1 and its downstream target GLUT1.
F-FDG-PET can be used to predict K19 expression in hepatocellular carcinoma and should thereby aid in the development of novel therapeutic strategies targeting K19
HCC-CSCs.
. |
| doi_str_mv | 10.1158/1078-0432.CCR-16-0871 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed</sourceid><recordid>TN_cdi_pubmed_primary_27663597</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>27663597</sourcerecordid><originalsourceid>FETCH-pubmed_primary_276635973</originalsourceid><addsrcrecordid>eNqFj01OwzAQhb0A0fJzBNBcwMVu0iRdoqhRKjYIyroyjhOMbE9kx4gchruSIGDLakbvfaP3hpBrzlacb4pbzvKCsjRZr8rykfKMsiLnJ2T5py_IeQhvjPGUs_SMLNZ5liWbbb4kn_tGuUG3WopBowNs4V75aXfAt_QBgx70u4JSOKk8PA3KQqmMCXAXAko9gx3U0QoHterFgHJyoxF-OvFSO7QCnsMM8QIqWpmIHhuFH2NnosSg4DvDT9E7q0OYOxzQYudF_zpektNWmKCufuYFual2h7KmfXyxqjn2Xlvhx-PvP8m_wBfiMV7y</addsrcrecordid><sourcetype>Index Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Identification of Keratin 19-Positive Cancer Stem Cells Associating Human Hepatocellular Carcinoma Using 18 F-Fluorodeoxyglucose Positron Emission Tomography</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>Alma/SFX Local Collection</source><source>EZB Electronic Journals Library</source><creator>Kawai, Takayuki ; Yasuchika, Kentaro ; Seo, Satoru ; Higashi, Tatsuya ; Ishii, Takamichi ; Miyauchi, Yuya ; Kojima, Hidenobu ; Yamaoka, Ryoya ; Katayama, Hokahiro ; Yoshitoshi, Elena Yukie ; Ogiso, Satoshi ; Kita, Sadahiko ; Yasuda, Katsutaro ; Fukumitsu, Ken ; Nakamoto, Yuji ; Hatano, Etsuro ; Uemoto, Shinji</creator><creatorcontrib>Kawai, Takayuki ; Yasuchika, Kentaro ; Seo, Satoru ; Higashi, Tatsuya ; Ishii, Takamichi ; Miyauchi, Yuya ; Kojima, Hidenobu ; Yamaoka, Ryoya ; Katayama, Hokahiro ; Yoshitoshi, Elena Yukie ; Ogiso, Satoshi ; Kita, Sadahiko ; Yasuda, Katsutaro ; Fukumitsu, Ken ; Nakamoto, Yuji ; Hatano, Etsuro ; Uemoto, Shinji</creatorcontrib><description>The current lack of tools for easy assessment of cancer stem cells (CSC) prevents the development of therapeutic strategies for hepatocellular carcinoma (HCC). We previously reported that keratin 19 (K19) is a novel HCC-CSC marker and that PET with
F-fluorodeoxyglucose (
F-FDG) is an effective method for predicting postoperative outcome in hepatocellular carcinoma. Herein, we examined whether K19
HCC-CSCs can be tracked using
F-FDG-PET.
K19 and glucose transporter-1 (GLUT1) expression was evaluated by IHC in 98 hepatocellular carcinoma patients who underwent
F-FDG-PET scans before primary tumor resection. Standardized uptake values (SUV) for primary tumors and tumor-to-nontumor SUV ratios (TNR) were calculated using FDG accumulation levels, and values were compared among K19
/K19
patients. Using hepatocellular carcinoma cell lines encoding with a K19 promoter-driven enhanced GFP,
F-FDG uptake and GLUT1 expression were examined in FACS-isolated K19
/K19
cells.
In hepatocellular carcinoma patients, K19 expression was significantly correlated with GLUT1 expression and FDG accumulation. ROC analyses revealed that among preoperative clinical factors, TNR was the most sensitive indicator of K19 expression in hepatocellular carcinoma tumors. In hepatocellular carcinoma cells, FACS-isolated K19
cells displayed significantly higher
F-FDG uptake than K19
cells. Moreover, gain/loss-of-function experiments confirmed that K19 regulates
F-FDG uptake through TGFβ/Smad signaling, including Sp1 and its downstream target GLUT1.
F-FDG-PET can be used to predict K19 expression in hepatocellular carcinoma and should thereby aid in the development of novel therapeutic strategies targeting K19
HCC-CSCs.
.</description><identifier>ISSN: 1078-0432</identifier><identifier>DOI: 10.1158/1078-0432.CCR-16-0871</identifier><identifier>PMID: 27663597</identifier><language>eng</language><publisher>United States</publisher><subject>Adult ; Aged ; Carcinoma, Hepatocellular - diagnostic imaging ; Carcinoma, Hepatocellular - genetics ; Carcinoma, Hepatocellular - pathology ; Female ; Fluorodeoxyglucose F18 - administration & dosage ; Gene Expression Regulation, Neoplastic ; Humans ; Keratin-19 - genetics ; Keratin-19 - isolation & purification ; Liver Neoplasms - diagnostic imaging ; Liver Neoplasms - genetics ; Liver Neoplasms - pathology ; Male ; Middle Aged ; Multimodal Imaging ; Neoplastic Stem Cells - pathology ; Prognosis ; Tomography, X-Ray Computed</subject><ispartof>Clinical cancer research, 2017-03, Vol.23 (6), p.1450</ispartof><rights>2016 American Association for Cancer Research.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27663597$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kawai, Takayuki</creatorcontrib><creatorcontrib>Yasuchika, Kentaro</creatorcontrib><creatorcontrib>Seo, Satoru</creatorcontrib><creatorcontrib>Higashi, Tatsuya</creatorcontrib><creatorcontrib>Ishii, Takamichi</creatorcontrib><creatorcontrib>Miyauchi, Yuya</creatorcontrib><creatorcontrib>Kojima, Hidenobu</creatorcontrib><creatorcontrib>Yamaoka, Ryoya</creatorcontrib><creatorcontrib>Katayama, Hokahiro</creatorcontrib><creatorcontrib>Yoshitoshi, Elena Yukie</creatorcontrib><creatorcontrib>Ogiso, Satoshi</creatorcontrib><creatorcontrib>Kita, Sadahiko</creatorcontrib><creatorcontrib>Yasuda, Katsutaro</creatorcontrib><creatorcontrib>Fukumitsu, Ken</creatorcontrib><creatorcontrib>Nakamoto, Yuji</creatorcontrib><creatorcontrib>Hatano, Etsuro</creatorcontrib><creatorcontrib>Uemoto, Shinji</creatorcontrib><title>Identification of Keratin 19-Positive Cancer Stem Cells Associating Human Hepatocellular Carcinoma Using 18 F-Fluorodeoxyglucose Positron Emission Tomography</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>The current lack of tools for easy assessment of cancer stem cells (CSC) prevents the development of therapeutic strategies for hepatocellular carcinoma (HCC). We previously reported that keratin 19 (K19) is a novel HCC-CSC marker and that PET with
F-fluorodeoxyglucose (
F-FDG) is an effective method for predicting postoperative outcome in hepatocellular carcinoma. Herein, we examined whether K19
HCC-CSCs can be tracked using
F-FDG-PET.
K19 and glucose transporter-1 (GLUT1) expression was evaluated by IHC in 98 hepatocellular carcinoma patients who underwent
F-FDG-PET scans before primary tumor resection. Standardized uptake values (SUV) for primary tumors and tumor-to-nontumor SUV ratios (TNR) were calculated using FDG accumulation levels, and values were compared among K19
/K19
patients. Using hepatocellular carcinoma cell lines encoding with a K19 promoter-driven enhanced GFP,
F-FDG uptake and GLUT1 expression were examined in FACS-isolated K19
/K19
cells.
In hepatocellular carcinoma patients, K19 expression was significantly correlated with GLUT1 expression and FDG accumulation. ROC analyses revealed that among preoperative clinical factors, TNR was the most sensitive indicator of K19 expression in hepatocellular carcinoma tumors. In hepatocellular carcinoma cells, FACS-isolated K19
cells displayed significantly higher
F-FDG uptake than K19
cells. Moreover, gain/loss-of-function experiments confirmed that K19 regulates
F-FDG uptake through TGFβ/Smad signaling, including Sp1 and its downstream target GLUT1.
F-FDG-PET can be used to predict K19 expression in hepatocellular carcinoma and should thereby aid in the development of novel therapeutic strategies targeting K19
HCC-CSCs.
.</description><subject>Adult</subject><subject>Aged</subject><subject>Carcinoma, Hepatocellular - diagnostic imaging</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Female</subject><subject>Fluorodeoxyglucose F18 - administration & dosage</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Keratin-19 - genetics</subject><subject>Keratin-19 - isolation & purification</subject><subject>Liver Neoplasms - diagnostic imaging</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - pathology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multimodal Imaging</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Prognosis</subject><subject>Tomography, X-Ray Computed</subject><issn>1078-0432</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFj01OwzAQhb0A0fJzBNBcwMVu0iRdoqhRKjYIyroyjhOMbE9kx4gchruSIGDLakbvfaP3hpBrzlacb4pbzvKCsjRZr8rykfKMsiLnJ2T5py_IeQhvjPGUs_SMLNZ5liWbbb4kn_tGuUG3WopBowNs4V75aXfAt_QBgx70u4JSOKk8PA3KQqmMCXAXAko9gx3U0QoHterFgHJyoxF-OvFSO7QCnsMM8QIqWpmIHhuFH2NnosSg4DvDT9E7q0OYOxzQYudF_zpektNWmKCufuYFual2h7KmfXyxqjn2Xlvhx-PvP8m_wBfiMV7y</recordid><startdate>20170315</startdate><enddate>20170315</enddate><creator>Kawai, Takayuki</creator><creator>Yasuchika, Kentaro</creator><creator>Seo, Satoru</creator><creator>Higashi, Tatsuya</creator><creator>Ishii, Takamichi</creator><creator>Miyauchi, Yuya</creator><creator>Kojima, Hidenobu</creator><creator>Yamaoka, Ryoya</creator><creator>Katayama, Hokahiro</creator><creator>Yoshitoshi, Elena Yukie</creator><creator>Ogiso, Satoshi</creator><creator>Kita, Sadahiko</creator><creator>Yasuda, Katsutaro</creator><creator>Fukumitsu, Ken</creator><creator>Nakamoto, Yuji</creator><creator>Hatano, Etsuro</creator><creator>Uemoto, Shinji</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20170315</creationdate><title>Identification of Keratin 19-Positive Cancer Stem Cells Associating Human Hepatocellular Carcinoma Using 18 F-Fluorodeoxyglucose Positron Emission Tomography</title><author>Kawai, Takayuki ; Yasuchika, Kentaro ; Seo, Satoru ; Higashi, Tatsuya ; Ishii, Takamichi ; Miyauchi, Yuya ; Kojima, Hidenobu ; Yamaoka, Ryoya ; Katayama, Hokahiro ; Yoshitoshi, Elena Yukie ; Ogiso, Satoshi ; Kita, Sadahiko ; Yasuda, Katsutaro ; Fukumitsu, Ken ; Nakamoto, Yuji ; Hatano, Etsuro ; Uemoto, Shinji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmed_primary_276635973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Carcinoma, Hepatocellular - diagnostic imaging</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Female</topic><topic>Fluorodeoxyglucose F18 - administration & dosage</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Keratin-19 - genetics</topic><topic>Keratin-19 - isolation & purification</topic><topic>Liver Neoplasms - diagnostic imaging</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - pathology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multimodal Imaging</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Prognosis</topic><topic>Tomography, X-Ray Computed</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kawai, Takayuki</creatorcontrib><creatorcontrib>Yasuchika, Kentaro</creatorcontrib><creatorcontrib>Seo, Satoru</creatorcontrib><creatorcontrib>Higashi, Tatsuya</creatorcontrib><creatorcontrib>Ishii, Takamichi</creatorcontrib><creatorcontrib>Miyauchi, Yuya</creatorcontrib><creatorcontrib>Kojima, Hidenobu</creatorcontrib><creatorcontrib>Yamaoka, Ryoya</creatorcontrib><creatorcontrib>Katayama, Hokahiro</creatorcontrib><creatorcontrib>Yoshitoshi, Elena Yukie</creatorcontrib><creatorcontrib>Ogiso, Satoshi</creatorcontrib><creatorcontrib>Kita, Sadahiko</creatorcontrib><creatorcontrib>Yasuda, Katsutaro</creatorcontrib><creatorcontrib>Fukumitsu, Ken</creatorcontrib><creatorcontrib>Nakamoto, Yuji</creatorcontrib><creatorcontrib>Hatano, Etsuro</creatorcontrib><creatorcontrib>Uemoto, Shinji</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kawai, Takayuki</au><au>Yasuchika, Kentaro</au><au>Seo, Satoru</au><au>Higashi, Tatsuya</au><au>Ishii, Takamichi</au><au>Miyauchi, Yuya</au><au>Kojima, Hidenobu</au><au>Yamaoka, Ryoya</au><au>Katayama, Hokahiro</au><au>Yoshitoshi, Elena Yukie</au><au>Ogiso, Satoshi</au><au>Kita, Sadahiko</au><au>Yasuda, Katsutaro</au><au>Fukumitsu, Ken</au><au>Nakamoto, Yuji</au><au>Hatano, Etsuro</au><au>Uemoto, Shinji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of Keratin 19-Positive Cancer Stem Cells Associating Human Hepatocellular Carcinoma Using 18 F-Fluorodeoxyglucose Positron Emission Tomography</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2017-03-15</date><risdate>2017</risdate><volume>23</volume><issue>6</issue><spage>1450</spage><pages>1450-</pages><issn>1078-0432</issn><abstract>The current lack of tools for easy assessment of cancer stem cells (CSC) prevents the development of therapeutic strategies for hepatocellular carcinoma (HCC). We previously reported that keratin 19 (K19) is a novel HCC-CSC marker and that PET with
F-fluorodeoxyglucose (
F-FDG) is an effective method for predicting postoperative outcome in hepatocellular carcinoma. Herein, we examined whether K19
HCC-CSCs can be tracked using
F-FDG-PET.
K19 and glucose transporter-1 (GLUT1) expression was evaluated by IHC in 98 hepatocellular carcinoma patients who underwent
F-FDG-PET scans before primary tumor resection. Standardized uptake values (SUV) for primary tumors and tumor-to-nontumor SUV ratios (TNR) were calculated using FDG accumulation levels, and values were compared among K19
/K19
patients. Using hepatocellular carcinoma cell lines encoding with a K19 promoter-driven enhanced GFP,
F-FDG uptake and GLUT1 expression were examined in FACS-isolated K19
/K19
cells.
In hepatocellular carcinoma patients, K19 expression was significantly correlated with GLUT1 expression and FDG accumulation. ROC analyses revealed that among preoperative clinical factors, TNR was the most sensitive indicator of K19 expression in hepatocellular carcinoma tumors. In hepatocellular carcinoma cells, FACS-isolated K19
cells displayed significantly higher
F-FDG uptake than K19
cells. Moreover, gain/loss-of-function experiments confirmed that K19 regulates
F-FDG uptake through TGFβ/Smad signaling, including Sp1 and its downstream target GLUT1.
F-FDG-PET can be used to predict K19 expression in hepatocellular carcinoma and should thereby aid in the development of novel therapeutic strategies targeting K19
HCC-CSCs.
.</abstract><cop>United States</cop><pmid>27663597</pmid><doi>10.1158/1078-0432.CCR-16-0871</doi></addata></record> |
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| ispartof | Clinical cancer research, 2017-03, Vol.23 (6), p.1450 |
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| source | MEDLINE; American Association for Cancer Research; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | Adult Aged Carcinoma, Hepatocellular - diagnostic imaging Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - pathology Female Fluorodeoxyglucose F18 - administration & dosage Gene Expression Regulation, Neoplastic Humans Keratin-19 - genetics Keratin-19 - isolation & purification Liver Neoplasms - diagnostic imaging Liver Neoplasms - genetics Liver Neoplasms - pathology Male Middle Aged Multimodal Imaging Neoplastic Stem Cells - pathology Prognosis Tomography, X-Ray Computed |
| title | Identification of Keratin 19-Positive Cancer Stem Cells Associating Human Hepatocellular Carcinoma Using 18 F-Fluorodeoxyglucose Positron Emission Tomography |
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