title: The impact of adhesion peptides within hydrogels on the phenotype and signaling of normal and cancerous mammary epithelial cells.
abstract: The microenviroment contributes to directing mammary epithelial cell (MEC) development and the progression of breast cancer. Three-dimensional culture models have been used to support formation of structures that display varying degrees of disorganization that parallel the degree of cancer. Synthetic hydrogels were employed to investigate the mechanisms by which specific adhesion signals in the microenvironment directed development. Polyethylene glycol-based hydrogels supported 3D growth of MECs and directed formation of a range of phenotypes that were functions of genotype, and identity and concentration of adhesion peptides RGD and YIGSR. Non-cancerous and cancerous MECs responded differentially to the same adhesion cues and produced variable structural organizations. An analysis of dynamic signaling pathways revealed differential activities of transcription factors within the MAPK and JAK/STAT pathways in response to genotype and adhesion. These results directly implicate adhesion in cancer development and demonstrate that AP1, CREB, STAT1, and STAT3 all contribute to the genotype dependence of cellular response to adhesion peptides. The tools presented in this work could be applied to other systems and connect extracellular cues with intracellular signaling to molecularly dissect tissue development and further biomaterials development.
authors.affiliation: Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208-3120, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Weiss
authors.forename: Beatriz Peñalver
authors.initials: BP
authors.lastname: Bernabé
authors.forename: Ariella
authors.initials: A
authors.lastname: Shikanov
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Bluver
authors.forename: Michael D
authors.initials: MD
authors.lastname: Mui
authors.forename: Seungjin
authors.initials: S
authors.lastname: Shin
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Broadbelt
authors.forename: Lonnie D
authors.initials: LD
authors.lastname: Shea
mesh_terms: D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology*; D005260:Female; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology*; D042361:Mammary Glands, Human / Q000473:pathology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010641:Phenotype; D011092:Polyethylene Glycols / Q000494:pharmacology; D012044:Regression Analysis; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D020100:Hydrogels; D010455:Peptides; D011092:Polyethylene Glycols