Surgery-induced wound response promotes stem-like and tumor-initiating features of breast cancer cells, via STAT3 signaling

Ilenia Segatto, Stefania Berton, Maura Sonego, Samuele Massarut, Tiziana Perin, Erica Piccoli, Alfonso Colombatti, Andrea Vecchione, Gustavo Baldassarre, Barbara Belletti

Research output: Contribution to journalArticlepeer-review

Abstract

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 stemlike 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.

Original languageEnglish
Pages (from-to)6267-6279
Number of pages13
JournalOncotarget
Volume5
Issue number15
Publication statusPublished - 2014

Keywords

  • Breast cancer
  • Cancer stem cells
  • CSC-like properties
  • STAT3
  • Tumor initiating cells

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

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