Abstract
BackgroundGreater than 50,000 new cases of breast cancer cases were diagnosed in Italy during 2013, with nearly 15,000 women succumbing to the disease. These epidemiological statistics highlight the overwhelming clinical dilemma of breast cancer and emphasize the need for novel therapeutic targets and prevention strategies. Countless studies in the fields of mammary gland development and breast cancer have led to an appreciation of a breast tumor microenvironment that actively contributes to the heterogeneous nature of breast cancer.MethodsThe current review will focus on the impact of IL-6 and in the breast tumor microenvironment. Excessive IL-6 has been demonstrated in primary breast tumors and breast cancer patient sera and is associated with poor clinical outcomes in breast cancer. These clinical associations are corroborated by emerging preclinical data revealing that IL-6 is a potent growth factor and promotes an epithelial-mesenchyme (EMT) phenotype in breast cancer cells to indicate that IL-6 in the breast tumor microenvironment is clinically relevant.ResultsHigh serum levels of interleukin-6 correlate with poor outcome in breast cancer patients. However, few data are yet available on the relationship between IL-6 and stem/progenitor cells, which may fuel the genesis of breast cancer in vivo. Mammospheres (MS) from node invasive breast carcinoma tissues express IL-6 mRNA at higher levels than MS from matched non-neoplastic mammary glands. IL-6 mRNA is detectable only in basal-like breast carcinoma tissues; our results reveal that IL-6 triggers a Notch-3-dependent upregulation of the Notch ligand Jagged-1, whose interaction with Notch-3 promotes the growth of MS and Michigan Cancer Foundation-7 (MCF-7)-derived spheroids. IL-6 induces a Notch-3-dependent upregulation of the carbonic anhydrase IX gene and promotes a hypoxia-resistant/invasive phenotype in MCF-7 cells and MS.ConclusionsIn conclusion, our data support the hypothesis that IL-6 induces malignant features in Notch-3-expressing, stem/progenitor cells from human ductal breast carcinoma and normal mammary gland.
Highlights
Greater than 50,000 new cases of breast cancer cases were diagnosed in Italy during 2013, with nearly 15,000 women succumbing to the disease
In our study, we found that high Interleukin 6 (IL-6) serum levels in breast cancer patients are associated with poor outcome and by the accumulating evidence suggesting that IL-6 assumes a direct role in the upregulation of malignant features in breast cancer cells
We find that IL-6 mRNA levels are readily detected ex vivo only in CK-5 positive basal-like breast carcinoma tissues and how these tumors express high levels of stem regulatory gene Bmi-1
Summary
Greater than 50,000 new cases of breast cancer cases were diagnosed in Italy during 2013, with nearly 15,000 women succumbing to the disease. Cancer cells exposed to IL-6 or which secrete the cytokine as an autocrine factor, show malignant features, such as an enhanced capacity to invade the extracellular matrix and an increased drug resistance [5,6,7]. Based on these data, the inhibition of the IL-6/IL-6 receptor interaction with specific antibodies has been proposed as a support cancer therapy [8,9,10]. MS from breast cancer tissues have been shown to proliferate in vitro and generate tubule-alveolar structures composed of Sanguinetti et al World Journal of Surgical Oncology (2015) 13:129
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
