title: Cytoskeletal and junctional heterogeneity in mammary tumor cells and their possible significance in tumor progression.
abstract: Malignant breast cancers appear to metastasize first via the lymphatics to colonize regional lymph nodes, and then via the blood circulation to colonize distant organs. Using a rat mammary tumor model based on the 13762NF adenocarcinoma, evidence is presented that malignant cell subpopulations spread lymphatically to regional lymph nodes, then become blood-borne and metastasize to lungs. Using chromosome and cytokeratin markers to identify specific tumor cell subpopulations, tumor progression in this system appears to be associated with the appearance of a highly specialized, metastatic cell subpopulation. This highly malignant cell subpopulation is completely uncoupled by gap junctions when examined for gap-junctional communication, in contrast with less malignant subpopulations that show varying degrees of cell communication through gap junctions. Loss of cell-cell communication may be one of the epigenetic events that leads to the generation of tumor cell diversification and heterogeneity. In concert with host selective pressures, this could result in the evolution of highly malignant cell subpopulations with unique characteristics.
authors.affiliation: Dept. of Tumor Biology, University of Texas M.D. Anderson Hospital and Tumor Institute, Houston.
authors.forename: G L
authors.initials: GL
authors.lastname: Nicolson
authors.forename: R B
authors.initials: RB
authors.lastname: Lichtner
authors.forename: J E
authors.initials: JE
authors.lastname: Trosko
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000818:Animals; D003599:Cytoskeleton / Q000648:ultrastructure*; D005819:Genetic Markers / Q000032:analysis; D007365:Intercellular Junctions / Q000648:ultrastructure*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology*; D009362:Neoplasm Metastasis; D051381:Rats
chemical_list: D005819:Genetic Markers