TY - JOUR
T1 - Epithelial-stromal interaction 1 (EPSTI1) substitutes for peritumoral fibroblasts in the tumor microenvironment
AU - De Neergaard, Michala
AU - Kim, Jiyoung
AU - Villadsen, René
AU - Fridriksdóttir, Agla Jael Rubner
AU - Rank, Fritz
AU - Timmermans-Wielenga, Vera
AU - Langerød, Anita
AU - Børresen-Dale, Anne-Lise
AU - Petersen, Ole William
AU - Rønnov-Jessen, Lone
N1 - Keywords: Animals; Biological Assay; Breast Neoplasms; Cell Line, Tumor; Cell Nucleus; Epithelium; Female; Fibroblasts; Humans; Mesoderm; Mice; Neoplasm Proteins; Organ Specificity; RNA Interference
PY - 2010/3
Y1 - 2010/3
N2 - Tumor cells can activate stroma, yet the implication of this activation in terms of reciprocal induction of gene expression in tumor cells is poorly understood. Epithelial Stromal Interaction 1 (EPSTI1) is an interferon response gene originally isolated from heterotypic recombinant cultures of human breast cancer cells and activated breast myofibroblasts. Here we describe the first immunolocalization of EPSTI1 in normal and cancerous breast tissue, and we provide evidence for a role of this molecule in the regulation of tumor cell properties and epithelial-mesenchymal transition. In general, no EPSTI1 staining was observed in normal breast epithelial cells from reduction mammoplasties (n = 25). However, in carcinomas, staining was positive in 22 of 40 biopsies and inversely correlated with the level of differentiation. To address the function of EPSTI1, we expressed EPSTI1 ectopically in one cell line and silenced endogenous EPSTI1 by RNA interference in another. Irrespective of the experimental approach, EPSTI1 expression led to an increase in tumorsphere formation - a property associated with breast stem/progenitor cells. Most remarkably, we show that EPSTI1, by conveying spread of tumor cells, can replace peritumoral activated fibroblasts in a tumor environment assay. These observations implicate EPSTI1 as a hitherto unappreciated regulator of tumor cell properties.
AB - Tumor cells can activate stroma, yet the implication of this activation in terms of reciprocal induction of gene expression in tumor cells is poorly understood. Epithelial Stromal Interaction 1 (EPSTI1) is an interferon response gene originally isolated from heterotypic recombinant cultures of human breast cancer cells and activated breast myofibroblasts. Here we describe the first immunolocalization of EPSTI1 in normal and cancerous breast tissue, and we provide evidence for a role of this molecule in the regulation of tumor cell properties and epithelial-mesenchymal transition. In general, no EPSTI1 staining was observed in normal breast epithelial cells from reduction mammoplasties (n = 25). However, in carcinomas, staining was positive in 22 of 40 biopsies and inversely correlated with the level of differentiation. To address the function of EPSTI1, we expressed EPSTI1 ectopically in one cell line and silenced endogenous EPSTI1 by RNA interference in another. Irrespective of the experimental approach, EPSTI1 expression led to an increase in tumorsphere formation - a property associated with breast stem/progenitor cells. Most remarkably, we show that EPSTI1, by conveying spread of tumor cells, can replace peritumoral activated fibroblasts in a tumor environment assay. These observations implicate EPSTI1 as a hitherto unappreciated regulator of tumor cell properties.
U2 - 10.2353/ajpath.2010.090648
DO - 10.2353/ajpath.2010.090648
M3 - Journal article
C2 - 20133812
SN - 0002-9440
VL - 176
SP - 1229
EP - 1240
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 3
ER -
