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01.07.2016 | Original Paper | Ausgabe 7/2016

Medical Oncology 7/2016

Letrozole-induced functional changes in carcinoma-associated fibroblasts and their influence on breast cancer cell biology

Zeitschrift:
Medical Oncology > Ausgabe 7/2016
Autoren:
Kaifu Li, Hua Kang, Yajun Wang, Tao Hai, Guohua Rong, Haichen Sun
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s12032-016-0779-z) contains supplementary material, which is available to authorized users.

Abstract

Accumulating evidence suggests that carcinoma-associated fibroblasts (CAFs) influence the efficacy of endocrine therapy. Aromatase inhibitors inhibit the growth of breast tumors by inhibiting the synthesis of estrogen. However, it remains unknown whether the aromatase inhibitor letrozole has an additional impact on CAFs, which further influence the efficacy of endocrine therapy. Primary CAFs were isolated from primary estrogen receptor-positive human breast tumors. Estrogen-deprived culture medium was used to exclude the influence of steroids. In co-culture, primary cultured CAFs increased MCF7 cell adhesion, invasion, migration and proliferation, and letrozole treatment inhibited these increases, except for the increase in proliferation. In total, 258 up-regulated genes and 47 down-regulated genes with an absolute fold change >2 were identified in CAFs co-cultured with MCF7 cell after letrozole treatment. One up-regulated genes (POSTN) and seven down-regulated genes (CCL2, CCL5, CXCL1, IL-8, CXCL5, LEP and NGF) were further validated by real-time PCR. The changes in CCL2 and CXCL1 expression were further confirmed using an automated microscopic imaging-based, high content analysis platform. Although the results need further functional validation, this study is the first to describe the differential tumor-promoting phenotype of CAFs induced by letrozole and the associated gene expression alterations. Most importantly, our data revealed that down-regulation of several secreted factors (CCL2, CCL5, CXCL1 etc.) in CAFs might be partially responsible for the efficacy of letrozole.

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Zusatzmaterial
Supplementary material 1 (PDF 127 kb)
12032_2016_779_MOESM1_ESM.pdf
Supplementary material 2 (PDF 206 kb)
12032_2016_779_MOESM2_ESM.pdf
Supplementary material 3 (PDF 81 kb)
12032_2016_779_MOESM3_ESM.pdf
Supplementary material 4 (PDF 71 kb)
12032_2016_779_MOESM4_ESM.pdf
Supplementary material 5 (PDF 140 kb)
12032_2016_779_MOESM5_ESM.pdf
Supplementary material 6 (PDF 159 kb)
12032_2016_779_MOESM6_ESM.pdf
Literatur
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