Comparative profiling between primary colorectal carcinomas and metastases identifies heterogeneity on drug resistance.
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.
Department of Pathology, Qingyuan People's Hospital, Jinan University, Qingyuan 511518, China.
Feng
F
Luo
Department of Pathology, Qingyuan People's Hospital, Jinan University, Qingyuan 511518, China.
Jinbang
J
Li
Department of Pathology, Qingyuan People's Hospital, Jinan University, Qingyuan 511518, China.
Shigang
S
Wu
Department of Pathology, Qingyuan People's Hospital, Jinan University, Qingyuan 511518, China.
Xuefang
X
Wu
Department of Pathology, Qingyuan People's Hospital, Jinan University, Qingyuan 511518, China.
Meixiang
M
Chen
Department of Pathology, Medical College, Jinan University, Guangzhou 510632, China.
Xueyun
X
Zhong
Department of Pathology, Qingyuan People's Hospital, Jinan University, Qingyuan 511518, China.
Kunping
K
Liu
D000071916:AC133 Antigen / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D019098:Telomerase / Q000378:metabolism; D046888:Tissue Array Analysis; D051176:beta Catenin / Q000378:metabolism
D000071916:AC133 Antigen; C495270:CTNNB1 protein, human; C000606023:PROM1 protein, human; D051176:beta Catenin; C509186:TERT protein, human; D019098:Telomerase
EMT; WNT signaling pathway; cancer stem cells; colorectal cancer; drug resistance