Published online May 26, 2015. doi: 10.4331/wjbc.v6.i2.39
Peer-review started: January 28, 2015
First decision: March 6, 2015
Revised: March 18, 2015
Accepted: April 16, 2015
Article in press: April 20, 2015
Published online: May 26, 2015
Processing time: 114 Days and 4.6 Hours
Signaling within the tumor microenvironment has a critical role in cancer initiation and progression. Adipocytes, one of the major components of the breast microenvironment, have been shown to provide pro-tumorigenic signals that promote cancer cell proliferation and invasiveness in vitro and tumorigenicity in vivo. Adipocyte secreted factors such as leptin and interleukin-6 (IL-6) have a paracrine effect on breast cancer cells. In adipocyte-adjacent breast cancer cells, the leptin and IL-6 signaling pathways activate janus kinase 2/signal transducer and activator of transcription 5, promoting the epithelial-mesenchymal transition, and upregulating stemness regulators such as Notch, Wnt and the Sex determining region Y-box 2/octamer binding transcription factor 4/Nanog signaling axis. In this review we will summarize the major signaling pathways that regulate cancer stem cells in breast cancer and describe the effects that adipocyte secreted IL-6 and leptin have on breast cancer stem cell signaling. Finally we will introduce a new potential treatment paradigm of inhibiting the adipocyte-breast cancer cell signaling via targeting the IL-6 or leptin pathways.
Core tip: We discuss the relationship between adipocytes in the microenvironment and breast cancer cells. We emphasize the role of adipocyte-secreted leptin and interleukin-6 in inducing breast cancer cell epithelial-mesenchymal transition and activating stemness pathways. Finally we summarize possible microenvironmental therapeutic targets and the potential role of non-coding RNAs in adipocyte-breast cancer interactions.