Raising an Antibody Specific to Breast Cancer Subpopulations Using Phage Display on Tissue Sections

TY - JOUR

T1 - Raising an Antibody Specific to Breast Cancer Subpopulations Using Phage Display on Tissue Sections

AU - Larsen, Simon Asbjørn

AU - Meldgaard, Theresa

AU - Fridriksdottir, Agla Jael Rubner

AU - Lykkemark, Simon

AU - Poulsen, Pi Camilla

AU - Overgaard, Laura Falkensteen

AU - Petersen, Helene Bundgaard

AU - Petersen, Ole William

AU - Kristensen, Peter

N1 - Copyright© 2016, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - BACKGROUND/AIM: Primary tumors display a great level of intra-tumor heterogeneity in breast cancer. The current lack of prognostic and predictive biomarkers limits accurate stratification and the ability to predict response to therapy. The aim of the present study was to select recombinant antibody fragments specific against breast cancer subpopulations, aiding the discovery of novel biomarkers.MATERIALS AND METHODS: Recombinant antibody fragments were selected by phage display. A novel shadowstick technology enabled the direct selection using tissue sections of antibody fragments specific against small subpopulations of breast cancer cells. Selections were performed against a subpopulation of breast cancer cells expressing CD271(+), as these previously have been indicated to be potential breast cancer stem cells. The selected antibody fragments were screened by phage ELISA on both breast cancer and myoepithelial cells. The antibody fragments were validated and evaluated by immunohistochemistry experiments.RESULTS: Our study revealed an antibody fragment, LH8, specific for breast cancer cells. Immunohistochemistry results indicate that this particular antibody fragment binds an antigen that exhibits differential expression in different breast cancer subpopulations.CONCLUSION: Further studies characterizing this antibody fragment, the subpopulation it binds and the cognate antigen may unearth novel biomarkers of clinical relevance.

AB - BACKGROUND/AIM: Primary tumors display a great level of intra-tumor heterogeneity in breast cancer. The current lack of prognostic and predictive biomarkers limits accurate stratification and the ability to predict response to therapy. The aim of the present study was to select recombinant antibody fragments specific against breast cancer subpopulations, aiding the discovery of novel biomarkers.MATERIALS AND METHODS: Recombinant antibody fragments were selected by phage display. A novel shadowstick technology enabled the direct selection using tissue sections of antibody fragments specific against small subpopulations of breast cancer cells. Selections were performed against a subpopulation of breast cancer cells expressing CD271(+), as these previously have been indicated to be potential breast cancer stem cells. The selected antibody fragments were screened by phage ELISA on both breast cancer and myoepithelial cells. The antibody fragments were validated and evaluated by immunohistochemistry experiments.RESULTS: Our study revealed an antibody fragment, LH8, specific for breast cancer cells. Immunohistochemistry results indicate that this particular antibody fragment binds an antigen that exhibits differential expression in different breast cancer subpopulations.CONCLUSION: Further studies characterizing this antibody fragment, the subpopulation it binds and the cognate antigen may unearth novel biomarkers of clinical relevance.

M3 - Journal article

C2 - 26708596

SN - 1109-6535

VL - 13

SP - 21

EP - 30

JO - Cancer Genomics & Proteomics

JF - Cancer Genomics & Proteomics

IS - 1

ER -