Circulating levels of transforming growth factor-βeta (TGF-β) and Chemokine (C-X-C Motif) Ligand-1 (CXCL1) as predictors of distant seeding of circulating tumor cells in patients with metastatic breast cancer

Rosa Divella, Antonella Daniele, Eufemia Savino, Fabiola Palma, Antonia Bellizzi, Francesco Giotta, Giovanni Simone, Marco Lioce, Michele Quaranta, Angelo Paradiso, Antonio Mazzocca

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The presence of circulating tumor cells (CTCs) in the peripheral blood is a prerequisite for the formation of distant metastases. Transforming growth factor-βeta (TGF-β) and Chemokine (C-X-C Motif) Ligand-1 (CXCL1) are cytokines involved in the colonization of distant sites by CTCs in several pre-clinical animal models. However, their role is poorly-investigated in patients with metastatic cancer. Here, we investigated whether circulating levels of TGF-β and CXCL1 are predictors of CTC seeding in preferential distant sites in patients with metastatic breast cancer. Materials and Methods: CTCs were isolated from the peripheral blood of 61 patients with metastatic breast cancer by immunomagnetic separation. Plasma samples were collected from the same patients and assayed for TGF-β and CXCL1 by enzyme-linked immunoassay. Results: Patients were grouped in CK1 +/- (N+ (N≥10+ (N≥50), according to the number (N) of cytokeratin 7/8-positive CTCs: the highest number of CK7/8-positive CTCs was detected in patients with negative Human epidermal growth factor receptor-2 (HER-2/NEU) status (p+ CTCs and plasma concentrations of TGF-β and CXCL1 higher than the median value had a poor prognosis in comparison to patients with CK1+/- CTCs and TGF-β and CXCL1 concentrations below the median value. Conclusion: Our study shows that elevated circulating levels of TGF-β and CXCL1 are associated with a poor prognosis, and higher detection of CTCs and propensity of these cells to seed lung metastases in patients with breast cancer.

Original languageEnglish
Pages (from-to)1491-1498
Number of pages8
JournalAnticancer Research
Volume33
Issue number4
Publication statusPublished - Apr 2013

Keywords

  • Breast cancer
  • Chemokines
  • Circulating tumor cells
  • CXCL1
  • Cytokines
  • Metastasis
  • TGF-β

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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