Abstract
Cancer associated fibroblasts (CAFs) play a main role in breast cancer progression and metastasis. Estrogens modulate in breast CAFs the expression of microRNAs (miRNAs) that are involved in the development of many tumors. In order to provide novel insights on the regulation of miRNAs by estrogens in breast cancer, we analyzed the expression of 754 miRNAs in CAFs obtained from primary mammary tumors and CAFs derived from a cutaneous breast cancer metastasis. Using the TaqMan™ Human MicroRNA Array, we found that 17β-estradiol (E2) modulates numerous peculiar and common miRNAs in CAFs derived from primary and the metastatic malignancies. In particular, we assessed that E2 modulates 133 miRNAs (41 up and 92 downregulated) in CAFs derived from primary breast tumors, whereas E2 modulates 415 miRNAs (399 up and 16 downregulated) in CAFs derived from a cutaneous metastasis of breast carcinoma. Therefore, a number of miRNAs three times higher in metastatic CAFs with respect to primary breast CAFs was found modulated by E2. Our findings shed new light on the cumulative regulation of miRNAs by E2 in the main players of the tumor microenvironment as CAFs. Moreover, our data may be taken into consideration that is useful toward innovative prognostic and therapeutic approaches in breast cancer progression.
Highlights
Breast cancer is the most common type of neoplasia and the primary cause of cancer mortality in women [1]
In order to provide novel findings on the potential of estrogens to modulate the expression of miRNAs in breast cancer microenviroment toward the metastatic dissemination, we aimed to assess upon exposure to estrogens the miRNA expression landscape in cancer associated fibroblasts (CAFs) derived from primary breast tumors and CAFs obtained from a cutaneous metastasis of a mammary carcinoma
We began the present study evaluating in CAFs derived from breast tumors and CAFs obtained from a cutaneous metastasis of a mammary carcinoma, the estrogen regulation of 754
Summary
Breast cancer is the most common type of neoplasia and the primary cause of cancer mortality in women [1]. Deaths from breast tumors are mainly due to the metastatic dissemination of the malignant cells, a process that may occur in approximately 30% of patients [1]. It has been established that the interactions between breast cancer cells and the associated stroma play a crucial role in breast tumor progression and metastasis [3]. Previous studies have shown that CAFs are involved in all stages of tumorigenesis and their action may be associated with a poor survival outcome [6]. In this regard, it has been shown that secreting several factors, including interleukins, growth factors and collagen, CAFs may trigger the inflammatory microenvironment
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