Profilin 2 isoform expression is associated with lung metastasis of colorectal cancer according to a comprehensive gene expression study using a mouse model

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Lung metastasis is the second most common type of metastasis in colorectal cancer. Specific treatments for lung metastasis have not been developed since the underlying mechanisms are poorly understood. The present study aimed to elucidate the molecular basis of lung metastasis in colorectal cancer. In a mouse model, cell lines that were highly metastatic to the lungs were established by injecting colorectal cancer cells through the tail vein and removing them from the lungs. Differential gene expression comparing the transfected cells with their parental cells was investigated using DNA microarrays. The results were functionally interpreted using gene enrichment analysis and validated using reverse transcription‑quantitative PCR (RT‑qPCR). The isoforms of the identified genes were examined by melting curve analysis. The present study established colorectal cancer cell lines that were highly metastatic to the lungs. DNA microarray experiments revealed that genes (N‑cadherin, VE‑cadherin, Six4, Akt and VCAM1) involved in motility, proliferation and adhesion were upregulated, and genes (tissue inhibitor of metalloproteinase‑3 and PAX6) with tumor‑suppressive functions were downregulated in metastatic cells. Profilin 2 (PFN2) expression was upregulated in multiple metastatic cell lines using RT‑qPCR. Two PFN2 isoforms were overexpressed in metastatic cells. In vitro and in vivo models were established and genes associated with lung metastasis were identified to overcome the heterogeneity of the disease. Overall, aberrant PFN2 expression is unreported in lung metastasis in colorectal cancer. In the present study, two PFN2 isoforms with differential tissue distribution were upregulated in metastatic cells, suggesting that they promote lung metastasis in colorectal cancer.

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