The impact of adhesion peptides within hydrogels on the phenotype and signaling of normal and cancerous mammary epithelial cells

Michael S. Weiss; Beatriz Peñalver Bernabé; Ariella Shikanov; Dennis A. Bluver; Michael D. Mui; Seungjin Shin; Linda J. Broadbelt; Lonnie D. Shea

doi:10.1016/j.biomaterials.2012.01.055

The impact of adhesion peptides within hydrogels on the phenotype and signaling of normal and cancerous mammary epithelial cells

Michael S. Weiss, Beatriz Peñalver Bernabé, Ariella Shikanov, Dennis A. Bluver, Michael D. Mui, Seungjin Shin, Linda J. Broadbelt, Lonnie D. Shea^*

^*Corresponding author for this work

Chemical and Biological Engineering

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

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.

Original language	English (US)
Pages (from-to)	3548-3559
Number of pages	12
Journal	Biomaterials
Volume	33
Issue number	13
DOIs	https://doi.org/10.1016/j.biomaterials.2012.01.055
State	Published - May 2012

Funding

Viability measurements were made at the Northwestern University High Throughput Analysis Laboratory, confocal microscopy was performed at the Northwestern University Biological Imaging Facility, and bioluminescence imaging was performed at the Northwestern University Center for Advanced Molecular Imaging. We thank M. Dimri and the labs of H. Band and V. Band (University of Nebraska) for assistance with BME culture, A. Garcia (Georgia Institute of Technology) and J. Shepard for helpful discussions, and S. Seidlits for synthesis of PEG-VS. This work was funded by the National Institutes of Health (NIH; R21CA125285 , UL1DE019587 , PL1EB008542 , which supports the Biomaterials core of the Oncofertility Consortium Roadmap Grant) and the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust ,. MSW and BPB were both supported by an NIH training grant ( T32GM008449 ) and AS was supported by a Baxter Early Career Development Award.

Keywords

Adhesion
Cell signaling
Hydrogel
Signal transducing mediator

ASJC Scopus subject areas

Mechanics of Materials
Ceramics and Composites
Bioengineering
Biophysics
Biomaterials

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.biomaterials.2012.01.055

Cite this

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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.",

keywords = "Adhesion, Cell signaling, Hydrogel, Signal transducing mediator",

author = "Weiss, {Michael S.} and Bernab{\'e}, {Beatriz Pe{\~n}alver} and Ariella Shikanov and Bluver, {Dennis A.} and Mui, {Michael D.} and Seungjin Shin and Broadbelt, {Linda J.} and Shea, {Lonnie D.}",

note = "Funding Information: Viability measurements were made at the Northwestern University High Throughput Analysis Laboratory, confocal microscopy was performed at the Northwestern University Biological Imaging Facility, and bioluminescence imaging was performed at the Northwestern University Center for Advanced Molecular Imaging. We thank M. Dimri and the labs of H. Band and V. Band (University of Nebraska) for assistance with BME culture, A. Garcia (Georgia Institute of Technology) and J. Shepard for helpful discussions, and S. Seidlits for synthesis of PEG-VS. This work was funded by the National Institutes of Health (NIH; R21CA125285 , UL1DE019587 , PL1EB008542 , which supports the Biomaterials core of the Oncofertility Consortium Roadmap Grant) and the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust ,. MSW and BPB were both supported by an NIH training grant ( T32GM008449 ) and AS was supported by a Baxter Early Career Development Award. ",

year = "2012",

month = may,

doi = "10.1016/j.biomaterials.2012.01.055",

language = "English (US)",

volume = "33",

pages = "3548--3559",

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AU - Weiss, Michael S.

AU - Bernabé, Beatriz Peñalver

AU - Shikanov, Ariella

AU - Bluver, Dennis A.

AU - Mui, Michael D.

AU - Shin, Seungjin

AU - Broadbelt, Linda J.

AU - Shea, Lonnie D.

N1 - Funding Information: Viability measurements were made at the Northwestern University High Throughput Analysis Laboratory, confocal microscopy was performed at the Northwestern University Biological Imaging Facility, and bioluminescence imaging was performed at the Northwestern University Center for Advanced Molecular Imaging. We thank M. Dimri and the labs of H. Band and V. Band (University of Nebraska) for assistance with BME culture, A. Garcia (Georgia Institute of Technology) and J. Shepard for helpful discussions, and S. Seidlits for synthesis of PEG-VS. This work was funded by the National Institutes of Health (NIH; R21CA125285 , UL1DE019587 , PL1EB008542 , which supports the Biomaterials core of the Oncofertility Consortium Roadmap Grant) and the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust ,. MSW and BPB were both supported by an NIH training grant ( T32GM008449 ) and AS was supported by a Baxter Early Career Development Award.

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N2 - 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.

AB - 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.

KW - Adhesion

KW - Cell signaling

KW - Hydrogel

KW - Signal transducing mediator

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JF - Biomaterials

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ER -

The impact of adhesion peptides within hydrogels on the phenotype and signaling of normal and cancerous mammary epithelial cells

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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