title: Effects of different tissue microenvironments on gene expression in breast cancer cells.
abstract: In metastasis, circulating tumor cells penetrate the walls of blood vessels and enter the metastatic target tissue, thereby becoming exposed to novel and relatively unsupportive microenvironments. In the new microenvironments, the tumor cells often remain in a dormant state indefinitely and must adapt before they are able to successfully colonize the tissue. Very little is known about this adaptive process. We studied temporal changes in gene expression when breast cancer cells adapt to survive and grow on brain, bone marrow, and lung tissue maintained in an in vivo culture system, as models of the metastatic colonization of these tissues. We observed the transient activation of genes typically associated with homeostasis and stress during the initial stages of adaptation, followed by the activation of genes that mediate more advanced functions, such as elaboration of cell morphology and cell division, as the cells adapted to thrive in the host tissue microenvironment. We also observed the temporary induction of genes characteristic of the host tissue, which was particularly evident when tumor cells were grown on brain tissue. These early transient gene expression events suggest potential points of therapeutic intervention that are not evident in data from well-established tumors.
authors.affiliation: Vaccine Research Institute of San Diego, San Diego, California, United States of America.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Rondeau
authors.affiliation: Vaccine Research Institute of San Diego, San Diego, California, United States of America.
authors.forename: Parisa
authors.initials: P
authors.lastname: Abedinpour
authors.affiliation: Vaccine Research Institute of San Diego, San Diego, California, United States of America.
authors.forename: Prerak
authors.initials: P
authors.lastname: Desai
authors.affiliation: Vaccine Research Institute of San Diego, San Diego, California, United States of America.
authors.forename: Veronique T
authors.initials: VT
authors.lastname: Baron
authors.affiliation: Vaccine Research Institute of San Diego, San Diego, California, United States of America.
authors.forename: Per
authors.initials: P
authors.lastname: Borgstrom
authors.affiliation: Vaccine Research Institute of San Diego, San Diego, California, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Welsh
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor