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<p>Recent evidence suggests that red blood cells (RBCs) may actively regulate course of tumor disease, whereas red cell distribution width (RDW) might even serve as surrogate marker of tumor progression. Here, we investigated the clinical and molecular significance of RDW in breast (BrCa) and d’Amico high-risk prostate cancer (PCa) patients. Higher RDW (RDW<sup>high</sup>) was associated with metastatic disease, poorer survival, therapy resistance, elevated circulating tumor cell (CTC) counts, proinflammatory mediators profiles and some comorbidities such as cardiological disorders or diabetes. Gene expression analysis of primary tumors from patients characterized by RDW<sup>high</sup> revealed deregulation of genes involved in inflammation, immune modulation, cell adhesion, and migration. Using imaging flow cytometry (imFC), we identified for the first time direct RBC-CTC interactions (CTC<sup>RBC</sup>) in almost 9% of PCa patients. The presence of CTC<sup>RBC</sup> correlated with lymph node involvement and shorter time-to-biochemical recurrence. Those CTCs interacting with RBCs displayed predominantly epithelial phenotype and lacked protrusions. Collectively, these results provide clinical and molecular evidence that RBCs can modulate tumor progression both indirectly, potentially through systemic inflammation, and directly, via physical interactions with CTCs. Importantly, our findings highlight the potential of RDW, a routinely measured blood parameter, as a simple and clinically meaningful biomarker of tumor progression and dissemination.</p>

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Interplay between red blood cells and circulating tumor cells: clinical and molecular evidence of a putative pro-metastatic axis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月6日

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  • Julia Richert,
  • Marta Popęda,
  • Anna Muchlińska,
  • Robert Wenta,
  • Barbara Bollin-Matysiak,
  • Aleksandra Parteka,
  • Beata Pieczyńska-Uziębło,
  • Tomasz Kryczka,
  • Anna Żaczek,
  • Grażyna Suchodolska,
  • Elżbieta Senkus,
  • Marcin Matuszewski,
  • Kevin Miszewski,
  • Natalia Bednarz-Knoll

摘要

Recent evidence suggests that red blood cells (RBCs) may actively regulate course of tumor disease, whereas red cell distribution width (RDW) might even serve as surrogate marker of tumor progression. Here, we investigated the clinical and molecular significance of RDW in breast (BrCa) and d’Amico high-risk prostate cancer (PCa) patients. Higher RDW (RDWhigh) was associated with metastatic disease, poorer survival, therapy resistance, elevated circulating tumor cell (CTC) counts, proinflammatory mediators profiles and some comorbidities such as cardiological disorders or diabetes. Gene expression analysis of primary tumors from patients characterized by RDWhigh revealed deregulation of genes involved in inflammation, immune modulation, cell adhesion, and migration. Using imaging flow cytometry (imFC), we identified for the first time direct RBC-CTC interactions (CTCRBC) in almost 9% of PCa patients. The presence of CTCRBC correlated with lymph node involvement and shorter time-to-biochemical recurrence. Those CTCs interacting with RBCs displayed predominantly epithelial phenotype and lacked protrusions. Collectively, these results provide clinical and molecular evidence that RBCs can modulate tumor progression both indirectly, potentially through systemic inflammation, and directly, via physical interactions with CTCs. Importantly, our findings highlight the potential of RDW, a routinely measured blood parameter, as a simple and clinically meaningful biomarker of tumor progression and dissemination.