An novel role of sphingosine kinase-1 (SPHK1) in the invasion and metastasis of esophageal carcinoma
<p>Abstract</p> <p>Background</p> <p>Treatment failure for esophageal carcinoma is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in esophageal carcinoma...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2011-09-01
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| Series: | Journal of Translational Medicine |
| Online Access: | http://www.translational-medicine.com/content/9/1/157 |
| _version_ | 1818387076368826368 |
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| author | Zhang Yan-Lan Wu Shui-Yan Cao Bang-rong Zhou Zhuan Tao Yan-Fang Pan Jian Hu Shao-Yan Zhao Wen-Li Wang Jian Lou Guo-Liang Li Zhen Feng Xing Ni Jian |
| author_facet | Zhang Yan-Lan Wu Shui-Yan Cao Bang-rong Zhou Zhuan Tao Yan-Fang Pan Jian Hu Shao-Yan Zhao Wen-Li Wang Jian Lou Guo-Liang Li Zhen Feng Xing Ni Jian |
| author_sort | Zhang Yan-Lan |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Treatment failure for esophageal carcinoma is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in esophageal carcinoma cells <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>A metastasis model using a Matrigel invasion clonal selection approach was employed to establish a highly invasive subline EC9706-P4 from the esophageal carcinoma cell (ESCC) line EC9706. The differentially expressed genes of the subline and the parental cells determined by gene microarrays were further analyzed by RT-PCR and Western blotting.</p> <p>Results</p> <p>We identified <it>sphingosine kinase 1 (SPHK1) </it>as an invasion and metastasis-related gene of esophageal cancer. <it>SPHK1 </it>was overexpressed in the EC9706-P4 subline with high invasive capacity. Among six ESCC lines tested, KYSE2 and KYSE30 cells showed the highest <it>SPHK1 </it>mRNA and protein expressions as well as the most invasive phenotype. By Western blotting, in 7/12 cases (58%), SPHK1 expression was higher in esophageal carcinomas than in the companion normal tissue. In 23/30 cases (76%), SPHK1 protein expression was upregulated in the tumors compared to matched normal tissue by immunohistochemistry (IHC). Esophageal carcinoma tissue microarray analysis indicated that SPHK1 expression correlated with the depth of tumor invasion (<it>P </it>< 0.0001) and lymph node metastasis (<it>P </it>= 0.016). By Kaplan-Meier analysis, strong SPHK1 expression was significantly associated with clinical failure (<it>P </it>< 0.01), suggesting the involvement of SPHK1 in aggressiveness of human esophageal carcinoma. <it>SPHK1 </it>overexpression significantly increased the invasiveness of EC9706 cells <it>in vitro </it>and also increased EC9706 cell growth and spontaneous metastasis <it>in vivo</it>, promoting significant increases in tumor growth, tumor burden and spontaneous lung metastasis in nude mice. <it>SPHK1 </it>expression significantly correlated with the expression of many EGFR pathway genes associated with invasion of cancer cells. SPHK1 protein expression also significantly correlated with the phosphorylation of EGFR.</p> <p>Conclusion</p> <p>In summary, our data implicate <it>SPHK1 </it>in the metastasis of esophageal cancer. Our study also identified downstream mediators of SPHK1 in esophageal cancer cells that may mediate enhanced malignant behavior, and several of these mediators may be useful as therapeutic targets.</p> |
| first_indexed | 2024-12-14T04:04:11Z |
| format | Article |
| id | doaj.art-c00ba40059c44a75a5c53fe63e64179d |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-14T04:04:11Z |
| publishDate | 2011-09-01 |
| publisher | BMC |
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| series | Journal of Translational Medicine |
| spelling | doaj.art-c00ba40059c44a75a5c53fe63e64179d2022-12-21T23:17:52ZengBMCJournal of Translational Medicine1479-58762011-09-019115710.1186/1479-5876-9-157An novel role of sphingosine kinase-1 (SPHK1) in the invasion and metastasis of esophageal carcinomaZhang Yan-LanWu Shui-YanCao Bang-rongZhou ZhuanTao Yan-FangPan JianHu Shao-YanZhao Wen-LiWang JianLou Guo-LiangLi ZhenFeng XingNi Jian<p>Abstract</p> <p>Background</p> <p>Treatment failure for esophageal carcinoma is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in esophageal carcinoma cells <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>A metastasis model using a Matrigel invasion clonal selection approach was employed to establish a highly invasive subline EC9706-P4 from the esophageal carcinoma cell (ESCC) line EC9706. The differentially expressed genes of the subline and the parental cells determined by gene microarrays were further analyzed by RT-PCR and Western blotting.</p> <p>Results</p> <p>We identified <it>sphingosine kinase 1 (SPHK1) </it>as an invasion and metastasis-related gene of esophageal cancer. <it>SPHK1 </it>was overexpressed in the EC9706-P4 subline with high invasive capacity. Among six ESCC lines tested, KYSE2 and KYSE30 cells showed the highest <it>SPHK1 </it>mRNA and protein expressions as well as the most invasive phenotype. By Western blotting, in 7/12 cases (58%), SPHK1 expression was higher in esophageal carcinomas than in the companion normal tissue. In 23/30 cases (76%), SPHK1 protein expression was upregulated in the tumors compared to matched normal tissue by immunohistochemistry (IHC). Esophageal carcinoma tissue microarray analysis indicated that SPHK1 expression correlated with the depth of tumor invasion (<it>P </it>< 0.0001) and lymph node metastasis (<it>P </it>= 0.016). By Kaplan-Meier analysis, strong SPHK1 expression was significantly associated with clinical failure (<it>P </it>< 0.01), suggesting the involvement of SPHK1 in aggressiveness of human esophageal carcinoma. <it>SPHK1 </it>overexpression significantly increased the invasiveness of EC9706 cells <it>in vitro </it>and also increased EC9706 cell growth and spontaneous metastasis <it>in vivo</it>, promoting significant increases in tumor growth, tumor burden and spontaneous lung metastasis in nude mice. <it>SPHK1 </it>expression significantly correlated with the expression of many EGFR pathway genes associated with invasion of cancer cells. SPHK1 protein expression also significantly correlated with the phosphorylation of EGFR.</p> <p>Conclusion</p> <p>In summary, our data implicate <it>SPHK1 </it>in the metastasis of esophageal cancer. Our study also identified downstream mediators of SPHK1 in esophageal cancer cells that may mediate enhanced malignant behavior, and several of these mediators may be useful as therapeutic targets.</p>http://www.translational-medicine.com/content/9/1/157 |
| spellingShingle | Zhang Yan-Lan Wu Shui-Yan Cao Bang-rong Zhou Zhuan Tao Yan-Fang Pan Jian Hu Shao-Yan Zhao Wen-Li Wang Jian Lou Guo-Liang Li Zhen Feng Xing Ni Jian An novel role of sphingosine kinase-1 (SPHK1) in the invasion and metastasis of esophageal carcinoma Journal of Translational Medicine |
| title | An novel role of sphingosine kinase-1 (SPHK1) in the invasion and metastasis of esophageal carcinoma |
| title_full | An novel role of sphingosine kinase-1 (SPHK1) in the invasion and metastasis of esophageal carcinoma |
| title_fullStr | An novel role of sphingosine kinase-1 (SPHK1) in the invasion and metastasis of esophageal carcinoma |
| title_full_unstemmed | An novel role of sphingosine kinase-1 (SPHK1) in the invasion and metastasis of esophageal carcinoma |
| title_short | An novel role of sphingosine kinase-1 (SPHK1) in the invasion and metastasis of esophageal carcinoma |
| title_sort | novel role of sphingosine kinase 1 sphk1 in the invasion and metastasis of esophageal carcinoma |
| url | http://www.translational-medicine.com/content/9/1/157 |
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