Antiangiogenic agent sunitinib induces epithelial to mesenchymal transition and accelerates motility of colorectal cancer cells
| Autor: | Chisato Tomida, Takayuki Uchida, Takeshi Nikawa, Shigetada Teshima-Kondo, Hikaru Nagano, Ayako Ohno, Katsuya Hirasaka, Naoko Yamagishi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Epithelial-Mesenchymal Transition Indoles Colorectal cancer sunitinib VEGF receptor tyrosine kinase inhibitor Motility Angiogenesis Inhibitors evasive adaptation Biology General Biochemistry Genetics and Molecular Biology Metastasis 03 medical and health sciences 0302 clinical medicine Cell Movement Internal medicine Neuropilin 1 medicine Humans Pyrroles Epithelial–mesenchymal transition Sunitinib Mesenchymal stem cell General Medicine medicine.disease HCT116 Cells Phenotype Neuropilin-1 030104 developmental biology Receptors Vascular Endothelial Growth Factor 030220 oncology & carcinogenesis Cancer research Colorectal Neoplasms Transcriptome medicine.drug |
| Zdroj: | The Journal of Medical Investigation. 64(3-4):250-254 |
| ISSN: | 1349-6867 |
| Popis: | Although vascular endothelial growth factor receptor (VEGF-R)-targeted antiangiogenic agents are important treatment for a number of human malignancies, there is accumulating evidence that the therapies may promote disease progression, such as invasion and metastasis. How tumors become to promote their evasiveness remains fully uncertain. One of possible mechanisms for the adaptation may be a direct effect of VEGF-R inhibitors on tumor cells expressing VEGF-R. To elucidate a direct effect of VEGF-R-targeting drug (sunitinib), we established a human colorectal cancer cell model adapted to sunitinib. The sunitinib-conditioned cells showed a significant increase in cellular motility and migration activities, compared to the vehicle-treated control cells. Consistent with the phenotype, the sunitinib-conditioned cells decreased the expression levels of E-cadherin (an epithelial marker), while significantly increased the levels of Slug and Zeb1 (mesenchymal markers). Expression profiles of VEGF-R in the sunitinib-conditioned cells showed that only neuropilin-1 (NRP1) expression was significantly increased among all VEGF-R tested. Blockade of NRP1 using its antagonist clearly repressed the migration activation in sunitinib-conditioned cells, but not in the control cells. These results suggest that inhibition of VEGF-R on colorectal cancer cells can drive the epithelial-mesenchymal transition, leading to activation of cell motility in an NRP1-dependent manner. J. Med. Invest. 64: 250-254, August, 2017. |
| Databáze: | OpenAIRE |
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