Journal
ONCOTARGET
Volume 5, Issue 15, Pages 6267-6279Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.2195
Keywords
STAT3; breast cancer; cancer stem cells; tumor initiating cells; CSC-like properties
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Funding
- Italian Association for Cancer Research (AIRC) [IG 10459]
- CRO Intramural Grant
- Friuli Exchange Program
- Outgoing AIRC/Marie Curie International Fellowship in Cancer Research
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Inflammation is clinically linked to cancer but the mechanisms are not fully understood. Surgery itself elicits a range of inflammatory responses, suggesting that it could represent a perturbing factor in the process of local recurrence and/or metastasis formation. Post-surgery wound fluids (WF), drained from breast cancer patients, are rich in cytokines and growth factors, stimulate the in vitro growth of breast cancer cells and are potent activators of the STAT transcription factors. We wondered whether STAT signaling was functionally involved in the response of breast cancer cells to post-surgical inflammation. We discovered that WF induced the enrichment of breast cancer cells with stem-like phenotypes, via activation of STAT3. In vitro, WF highly stimulated mammosphere formation and self-renewal of breast cancer cells. In vivo, STAT3 signaling was critical for breast cancer cell tumorigenicity and for the formation of local relapse after surgery. Overall, we demonstrate here that surgery-induced inflammation promotes stem-like phenotypes and tumor-initiating abilities of breast cancer cells. Interfering with STAT3 signaling with a peri-surgical treatment is sufficient to strongly suppress this process. The understanding of the crosstalk between breast tumor-initiating cells and their microenvironment may open the way to successful targeting of these cells in their initial stages of growth and be eventually curative.
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