Complex Behavior of ALDH1A1 and IGFBP1 in Liver Metastasis from a Colorectal Cancer
| العنوان: | Complex Behavior of ALDH1A1 and IGFBP1 in Liver Metastasis from a Colorectal Cancer |
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| المؤلفون: | Ye Jin Ha, Ka Hee Tak, Tae Won Kim, Chan Wook Kim, Yong Sung Kim, Seon Ae Roh, Jin Cheon Kim, Seon-Young Kim, Seon-Kyu Kim, Dong-Hyung Cho |
| المصدر: | PLoS ONE PLoS ONE, Vol 11, Iss 5, p e0155160 (2016) PLOS ONE(11): 5 |
| بيانات النشر: | Public Library of Science (PLoS), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Physiology, Protein Expression, Cell, lcsh:Medicine, Vimentin, Metastasis, Mice, 0302 clinical medicine, Immune Physiology, Basic Cancer Research, Gene expression, Medicine and Health Sciences, lcsh:Science, Mice, Inbred BALB C, Multidisciplinary, Liver Neoplasms, Reverse transcription polymerase chain reaction, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cell lines, Heterografts, Biological cultures, Colorectal Neoplasms, Research Article, Mice, Nude, Surgical and Invasive Medical Procedures, Biology, Aldehyde Dehydrogenase 1 Family, Digestive System Procedures, 03 medical and health sciences, Cell Line, Tumor, Gene Expression and Vector Techniques, medicine, Animals, Humans, Molecular Biology Techniques, Molecular Biology, Immunohistochemistry Techniques, Cell Proliferation, Colorectal Cancer, Transplantation, Molecular Biology Assays and Analysis Techniques, Cadherin, Cell growth, lcsh:R, Cancers and Neoplasms, Biology and Life Sciences, Retinal Dehydrogenase, Organ Transplantation, Aldehyde Dehydrogenase, medicine.disease, Molecular biology, digestive system diseases, Liver Transplantation, Research and analysis methods, Histochemistry and Cytochemistry Techniques, Insulin-Like Growth Factor Binding Protein 1, SW480 cells, 030104 developmental biology, Immunologic Techniques, biology.protein, lcsh:Q, Spleen, Cloning |
| الوصف: | Using our data set (GSE50760) previously established by RNA sequencing, the present study aimed to identify upregulated genes associated with colorectal cancer (CRC) liver metastasis (CLM) and verify their biological behavior. The potential roles of candidate genes in tumors were assessed using cell proliferation and invasion assays. Tissue samples were collected from 18 CRC patients with synchronous CLM and two CRC cell lines (SW480 and SW620) were used for transfection and cloning. The roles of the genes identified in CLM were verified using immunohistochemistry in 48 nude mice after intrasplenic transplantation of CRC cells. mRNA and protein expression was determined by quantitative real-time reverse transcription polymerase chain reaction and western blot, respectively. Nine genes were initially selected according to the relevance of their molecular function and biological process and, finally, ALDH1A1 and IGFBP1 were chosen based on differential mRNA expression and a positive correlation with protein expression. The overexpression of ALDH1A1 and IGFBP1 significantly and time-dependently decreased cell proliferation (p ≤ 0.001-0.003) and suppressed invasiveness by ≥3-fold over control cells (p < 0.001) in the SW480 cell line, whereas they had a slight effect on reducing SW620 cell proliferation. The protein expression levels of E-cadherin, N-cadherin, claudin-1, and vimentin were significantly higher in CLM than in primary tumor tissues (p < 0.05). However, the cadherin switch, namely, N-cadherin overexpression with reduced E-cadherin expression, was not observed in CLM tissues and transfected CRC cells. Irrespective of reduced proliferation and invasion found on in vitro cell assays, persistent overexpression of β-catenin, vimentin, and ZO-1 in IGFBP1-overexpressing SW480 cells possibly contributed to CLM development in mice implanted with IGFBP1-overexpressing SW480 cells (CLM occurrences: SW480/IGFBP1-transfected mice vs. SW480/vector- and SW480/ALDH1A1-transfected mice, 4/8 vs. 0/10, p = 0.023). In conclusion, ALDH1A1 and IGFBP1 are differentially overexpressed in CLM and may play a dual role, functioning as both tumor suppressors and metastasis promoters in CRC. |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::69b51177795c3d919efc9e5d0e9e2a93Test https://doi.org/10.1371/journal.pone.0155160Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....69b51177795c3d919efc9e5d0e9e2a93 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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