Abnormal granulocyte differentiation and the paradoxical switch of transforming growth factor-β1 in breast cancer patients

Abstract

To analyze the characteristics of abnormal granulocytic differentiation in breast cancer patients and explore the role of TGF-β1 in granulocytic differentiation of hematopoietic stem cells (HSCs) and tumor development. Blood samples were collected from 52 patients with invasive ductal carcinoma and 47 healthy donors. The distribution of granulocytes was compared between the two groups and the effects of surgery and radiotherapy on granulocytes were analyzed. The relationship between granulocyte abnormalities and the clinicopathological characteristics of the patients was analyzed. Spleen hematopoietic stem cells isolated from normal and tumor-bearing mice were cultured and treated with TGF-β1, and colony formation of the myeloid cells was compared and the proportion of granulocytes was analyzed with flow cytometry. The white blood cell (WBC) count, neutrophils, total granulocytes, granulocyte ratio in the total WBCs, and neutrophil/lymphocyte ratio (NLR) were significantly increased (P < 0.05), while the eosinophils and its subpopulations were obviously decreased (P < 0.05) in breast cancer patients. Clone formation experiments showed that the numbers of CFU-GM, BFU-E and CFU-M colonies were significantly greater in the spleen cells from tumor-bearing mice than in those from normal mice (P < 0.05). TGF- β1 treatment obviously suppressed clone formation in spleen HSCs from normal mice but significantly promoted the proliferation and granulocyte differentiation of the spleen HSCs from tumor-bearing mice. Breast cancer patients have obvious abnormalities in granulocytic differentiation possibly as a result of hematopoietic stem cell differentiation imbalance induced by TGF-β1 and other growth factors produced by the tumor cells. TGF-β1 highlights a paradoxical shift in the regulation of clone formation and granulocytic differentiation of spleen hematopoietic stem cells.