Unexpected properties of endostatin-producing mouse BCR-ABL-transformed cells

• Published in: International journal of oncology Vol. 40; no. 2; pp. 487 - 493
• Main Authors: KRMENCIKOVA, Monika, STANEK, Libor, PETRACKOVA, Martina, DUNDR, Pavel, VONKA, Vladimír
• Format: Journal Article
• Language: English
• Published: Athens Editorial Academy of the International Journal of Oncology 01-02-2012
• Subjects: Animals; Biological and medical sciences; Cell Line, Transformed - metabolism; Cell Line, Transformed - pathology; Cell Line, Transformed - transplantation; Cell Proliferation; Cell Transformation, Neoplastic; Chromosome aberrations; Culture Media, Conditioned - pharmacology; Endostatins - metabolism; Endostatins - pharmacology; Endostatins - secretion; Female; Fusion Proteins, bcr-abl - genetics; Fusion Proteins, bcr-abl - metabolism; Histocompatibility Antigens Class I - metabolism; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - physiology; Kaplan-Meier Estimate; Medical genetics; Medical sciences; Mice; Mice, Inbred BALB C; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Transplantation; Tumors; Chromosomal aberration; Solid tumor; Transformed cell; Non-specific serine/threonine protein kinase; Endostatin; solid hematological tumors; Cell transformation; Carcinogenesis; Abnormal chromosome C9; Cancerology; Abnormal chromosome G22; Antiangiogenic agent; Hybrid gene; Chromosome translocation; Enzyme; Transferases; Rodentia; BCR-ABL; Malignant tumor; Philadelphia chromosome; Vertebrata; Mammalia; bcr gene; Mouse; Animal; C-Onc gene; Abnormal chromosome; Cancer
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.2011.1213

We investigated whether a genetic modification of BCR-ABL-transformed mouse cells that resulted in endostatin (ES) production altered their oncogenic potential. Mouse B210 cells, which express p210bcr-abl fusion protein and induce leukemia-like disease and extremely rarely solid tumors after intravenous (i.v.) administration, were used. The cells were transfected with a plasmid carrying genes for mouse ES and resistance to blasticidine. Transduced cells were isolated in media supplemented with blasticidine. Production of ES was determined by Western blotting. For further tests, two clones were selected, and their pathogenicity after i.v. inoculation was tested. Compared with the parental B210 cells, the capability of both gene-modified cell clones to induce lethal leukemia was reduced. However, mice that did not succumb to leukemia subsequently developed solid tumors. They were composed of poorly differentiated cells with irregular nuclei and roughly granular chromatin and were well vascularized. FISH revealed the presence of the BCR-ABL fusion gene both in tumors and spleens. Immunohistological investigation of the tumors demonstrated the production of ES in vivo and the cell lines derived from the tumors produced detectable amounts of ES, this demonstrating that the formation of solid tumors was not associated with the loss or silencing of the ES gene.