Implication of tyrosine kinase receptor and steel factor in cell density-dependent growth in cervical cancers and leukemias
Por:
Caceres-Cortes J.R., Alvarado-Moreno J.A., Waga K., Rangel-Corona R., Monroy-Garcia A., Rocha-Zavaleta L., Urdiales-Ramos J., Weiss-Steider B., Haman A., Hugo P., Brousseau R., Hoang T.
Publicada:
1 ene 2001
Resumen:
Cell-cell interaction is important in the expansion of leukemic cells and of solid tumors. Steel factor (SF) or Kit ligand is produced as a membrane-bound form (mSF) and a soluble form. Because both primary gynecological tumors and primary leukemic cells from patients with acute myeloblastic leukemia (AML) have been shown to coexpress c-Kit and SF, we addressed the question of whether mSF could contribute to cell interaction in these cancers. Investigations on primary cervical carcinomas have been hindered by the fact that the cells do not grow in culture. We report herein the establishment of two cervical carcinoma cell lines, CALO and INBL, that reproduce the pattern of SF/c-Kit expression observed in primary tumor samples. In addition, these cells exhibit marked density-dependent growth much in the same way as AML blasts. Using an antisense strategy with phosphorothioate-modified oligonucleotides that specifically target SF without affecting other surface markers, we provide direct evidence for a role of mSF and c-Kit in cell interaction and cell survival in these gynecological tumor cell lines as well as in primary AML blasts. Finally, our study defines the importance of juxtacrine stimulation, which may be as important, if not more, than autocrine stimulation in cancers.
Filiaciones:
Caceres-Cortes J.R.:
Laboratories of Oncology, Universidad Autonoma de Mexico, Mexico 15000, Mexico
Universidad Autonoma de Mexico, Mexico 15000, Mexico
Alvarado-Moreno J.A.:
Laboratories of Oncology, Universidad Autonoma de Mexico, Mexico 15000, Mexico
Universidad Autonoma de Mexico, Mexico 15000, Mexico
Monroy-Garcia A.:
Universidad Autonoma de Mexico, Mexico 15000, Mexico
Hoang T.:
Laboratory of Hemopoiesis and Leukemia, Clinical Research Institute of Montreal, Montreal, H2W 1R7, Quebec, Canada
Unit in Cell Differentiation and Cancer, Facultad de Estudios Superiores Zaragoza, Universidad Autonoma de Mexico, Mexico 15000, Mexico
Molecular Biology Department, Biomedical Research Institute, Universidad Autonoma de Mexico, Mexico 15000, Mexico
Institut de Recherches en Biotechnologie, Montreal, H4P 2R2 Quebec, Canada
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