Comparative profiling between primary colorectal carcinomas and metastases identifies heterogeneity on drug resistance
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Feng Luo1,*, Jinbang Li1,*, Shigang Wu1, Xuefang Wu1, Meixiang Chen1, Xueyun Zhong2, Kunping Liu1
1Department of Pathology, Qingyuan People’s Hospital, Jinan University, Qingyuan 511518, China
2Department of Pathology, Medical College, Jinan University, Guangzhou 510632, China
*These authors have contributed equally to this work
Kunping Liu, email: [email protected]
Xueyun Zhong, email: [email protected]
Keywords: colorectal cancer, drug resistance, WNT signaling pathway, EMT, cancer stem cells
Received: March 14, 2016 Accepted: August 11, 2016 Published: August 24, 2016
Metastases cause recurrence and mortality for patients with colorectal carcinomas (CRC). In present study, we evaluated heterogeneity on drug resistance and its underlying mechanism between metastatic and primary CRC. Immunohistochemical results from clinical tissue microarray (TMA) suggested that the expression concordance rates of cancer stem cells (CSCs) and drug resistance relative proteins between lymph-node metastatic and primary CRC foci were low. The apoptotic and proliferation indexes in metastasis CRC specimens were decreased compared with primary. In vitro experimental results indicated that the migration and invasion abilities were upregulated in metastatic cells SW620 compared with primary cells SW480, the cellular efflux ability and WNT/β-catenin activity were also upregulated in SW620 cells. After 5-fluorouracil (5-Fu) treatment, the reduction in the proportion of cell apoptosis, CD133 and TERT expression levels in SW620 were lower than that in SW480 cells. Bioinformatics analysis in whole-genome transcriptional profiling results between metastatic and primary CRC cells suggested that differentially expressed genes were mainly centered on well-characterized signaling pathways including WNT/β-catenin, cell cycle and cell junction. Collectively, heterogeneity of drug resistant was present between metastatic and primary CRC specimens and cell lines, the abnormal activation of WNT/β-catenin signaling pathway could be a potential molecular leading to drug resistant ability enhancing in metastatic CRC cells.
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