Nothing Special   »   [go: up one dir, main page]
IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland
Pasquale Sansone, … , Pasquale Chieco, Massimiliano Bonafè
Pasquale Sansone, … , Pasquale Chieco, Massimiliano Bonafè
Published December 3, 2007
Citation Information: J Clin Invest. 2007;117(12):3988-4002. https://doi.org/10.1172/JCI32533.
View: Text | PDF
Research Article

IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland

Abstract

High serum levels of IL-6 correlate with poor outcome in breast cancer patients. However, no data are available on the relationship between IL-6 and mammary stem/progenitor cells, which may fuel the genesis of breast cancer in vivo. Herein, we address this issue in the MCF-7 breast cancer cell line and in primary human mammospheres (MS), multicellular structures enriched in stem/progenitor cells of the mammary gland. MS from node invasive breast carcinoma tissues expressed IL-6 mRNA at higher levels than did MS from matched non-neoplastic mammary glands. In addition, IL-6 mRNA was detected only in basal-like breast carcinoma tissues, an aggressive breast carcinoma variant showing stem cell features. IL-6 treatment triggered Notch-3–dependent upregulation of the Notch ligand Jagged-1 and promotion of MS and MCF-7–derived spheroid growth. Moreover, IL-6 induced Notch-3–dependent upregulation of the carbonic anhydrase IX gene and promoted a hypoxia-resistant/invasive phenotype in MCF-7 cells and MS. Finally, autocrine IL-6 signaling relied upon Notch-3 activity to sustain the aggressive features of MCF-7–derived hypoxia-selected cells. In conclusion, these 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.

Authors

Pasquale Sansone, Gianluca Storci, Simona Tavolari, Tiziana Guarnieri, Catia Giovannini, Mario Taffurelli, Claudio Ceccarelli, Donatella Santini, Paola Paterini, Kenneth B. Marcu, Pasquale Chieco, Massimiliano Bonafè

×

Figure 1

IL-6 mRNA is expressed in MS and in basal-like breast carcinoma tissues.

Options: View larger image (or click on image) Download as PowerPoint
IL-6 mRNA is expressed in MS and in basal-like breast carcinoma tissues....
(A) Phase-contrast microscopy of day 10 primary T-MS generated from samples listed in Table 1. Scale bars: 100 μm. (B) RT-PCR analysis of IL-6, Bmi-1, CK-5, CD44, Oct-4, and β2μ mRNA in T-MS and in tumor tissues from which T-MS had been obtained. (C) Day 10 primary N-MS and T-MS were obtained from the same patient (see Table 1). RT-PCR analysis of IL-6, Bmi-1, CK-5, BCRP-1, and CD133 and quantitation of IL-6, Bmi-1, and CK-5 mRNA, first normalized onto β2μ mRNA and then expressed as a ratio of N-MS to T-MS. *P = 0.031, Mann-Whitney test. NA, not available. (D) Breast carcinoma tissues from patients affected by basal-like or ductal breast carcinoma (see Table 2) were subjected to RT-PCR analysis. Shown is the ratio of IL-6 to β2μ mRNA. #P = 0.001, Mann-Whitney test.