Chronic exposure of VEGF inhibitors promotes the malignant phenotype of colorectal cancer cells
| Autor: | Tomoki Abe, Takeshi Nikawa, Chisato Tomida, Katsuya Hirasaka, Chiaki Yano, Shigetada Teshima-Kondo, Ayako Ohno, Takayuki Uchida, Kana Aibara, Naoko Yamagishi |
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| Rok vydání: | 2015 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.drug_class Colorectal cancer Apoptosis Monoclonal antibody General Biochemistry Genetics and Molecular Biology Tyrosine-kinase inhibitor chemistry.chemical_compound Cell Movement medicine Humans Anilides malignant phenotype biology Cancer Foretinib General Medicine HCT116 Cells medicine.disease VEGF VEGF-targeting drugs Antibodies Neutralizing Phenotype Receptors Vascular Endothelial Growth Factor chemistry Cancer cell Immunology Quinolines Cancer research biology.protein colon cancer cells Antibody Colorectal Neoplasms |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1349-6867 1343-1420 |
| DOI: | 10.2152/jmi.62.75 |
| Popis: | 3 These authors contributed egually to this work. Abstract : VEGF-targeting anti-angiogenic drugs have enabled significant advances in cancer therapy. How- ever, acquired resistance to VEGF-targeting drugs occurs, leading to disease progression. How tumors become the resistance remains fully uncertain. One of possible mechanisms for the resistance may be the direct effect of VEGF inhibitors on tumor cells expressing VEGF receptors (VEGF-R). We investigated here the direct effect of chronic VEGF inhibition on phenotype changes in cancer cells. To chronically inhibit cancer cell-derived VEGF, human colon cancer HCT116 cells were chronically exposed (3 months) to anti-VEGF neutralizing monoclonal antibody (HCT/mAb cells, blockade of VEGF alone) or VEGF-R tyrosine kinase inhibitor foretinib (HCT/fore cells, blockade of all VEGF family). HCT/mAb cells redundantly increased VEGF family member (VEGF, PlGF, VEGF-B, VEGF-R1 and VEGF-R2) and induced a resistance to hypoxia-induced apoptosis. By contrast, HCT/fore cells did not show the redundant increase in VEGF family member, but significantly increased a VEGF-independent pro-angiogenic factor FGF-2. HCT/fore cells showed increased migration and invasion activities in addition to a resistance to hypoxia-induced apoptosis. The resistance to apoptosis was significantly suppressed by inhibition of hypoxia-inducible factor-1α in HCT/mAb cells, but not in HCT/fore cells. These findings suggest that chronic inhibition of VEGF/VEGF-R accelerates malignant phenotypes of colon cancer cells. J. Med. Invest. 62 : 75-79, February, 2015 |
| Databáze: | OpenAIRE |
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