Selection of a MCF-7 Breast Cancer Cell Subpopulation with High Sensitivity to IL-1β: Characterization of and Correlation between Morphological and Molecular Changes Leading to Increased Invasiveness.
Cancer and inflammation are closely related in tumor malignancy prognosis. Breast cancer MCF-7 cells have a poor invasive phenotype, although, under IL-1β stimulus, acquire invasive features. Cell response heterogeneity has precluded precise evaluation of the malignant transition. MCF-7A3 cells were selected for high sensitivity to IL-1β stimulus, uniform expression of CXCR4, and stability of IL1-RI. Structural changes, colony formation ability, proliferation rate, chemotaxis, Matrigel invasion, E-cadherin mRNA expression and protein localization were determined in these cells and in MCF-7 parental cells under the stimulus of IL-1β. Selected MCF-7A3 cells showed a uniform response to IL-1β stimulation increasing features of invasive cells such as scattering, colony formation, proliferation, chemokinesis and invasion. Basal expression of E-cadherin mRNA was higher, and IL-1β stimulus had no further effect at early times of cytokine exposure. Total E-cadherin levels remained unchanged in parental cells, whereas levels decreased, as MCF-7A3 cells became fibroblastoid or scattered. Triton X-100 soluble/insoluble E-cadherin ratios were highly increased in these cells, while, in MCF-7pl cells, ratios could not be correlated with morphology changes. MCF-7A3 cells uniform response to IL-1β allowed characterization of changes induced by the cytokine that had not been assessed when using heterogeneous cell lines.
Department of Molecular Biomedicine, Center for Research and Advanced Studies of the National Polytechnic Institute, 2508 Instituto Politecnico Nacional Avenue, 07360 Mexico City, Mexico.
Eloy Andres
EA
Pérez-Yépez
Jorge-Tonatiuh
JT
Ayala-Sumuano
Alicia Maria
AM
Reveles-Espinoza
Isaura
I
Meza