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J Cancer Res Clin Oncol. 2018 Jul;144(7):1253-1263. doi: 10.1007/s00432-018-2646-0. Epub 2018 May 3.

Tumor cell expression of CD163 is associated to postoperative radiotherapy and poor prognosis in patients with breast cancer treated with breast-conserving surgery.

Author information

1
Divison of Neurobiology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
2
Department of Clinical Pathology, Centre for Diagnostics, Region Östergötland, Linköping, Sweden.
3
Department of Pathology, County Hospital Ryhov, Jönköping, Sweden.
4
Departement of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
5
Division of Surgery, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
6
Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
7
Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 77, Stockholm, Sweden. Ivan.Shabo@ki.se.
8
Department of Breast, Endocrine and Sarcoma Surgery, Karolinska University Hospital, Stockholm, Sweden. Ivan.Shabo@ki.se.

Abstract

PURPOSE:

Cancer cell fusion with macrophages results in highly tumorigenic hybrids that acquire genetic and phenotypic characteristics from both maternal cells. Macrophage traits, exemplified by CD163 expression, in tumor cells are associated with advanced stages and poor prognosis in breast cancer (BC). In vitro data suggest that cancer cells expressing CD163 acquire radioresistance.

METHODS:

Tissue microarray was constructed from primary BC obtained from 83 patients treated with breast-conserving surgery, 50% having received postoperative radiotherapy (RT) and none of the patients had lymph node or distant metastasis. Immunostaining of CD163 in cancer cells and macrophage infiltration (MI) in tumor stroma were evaluated. Macrophage:MCF-7 hybrids were generated by spontaneous in vitro cell fusion. After irradiation (0, 2.5 and 5 Gy γ-radiation), both hybrids and their maternal MCF-7 cells were examined by clonogenic survival.

RESULTS:

CD163-expression by cancer cells was significantly associated with MI and clinicopathological data. Patients with CD163-positive tumors had significantly shorter disease-free survival (DFS) after RT. In vitro generated macrophage:MCF-7 hybrids developed radioresistance and exhibited better survival and colony forming ability after radiation compared to maternal MCF-7 cancer cells.

CONCLUSIONS:

Our results suggest that macrophage phenotype in tumor cells results in radioresistance in breast cancer and shorter DFS after radiotherapy.

KEYWORDS:

Breast cancer; CD163; Radiotherapy; Treatment resistance; Tumor-associated macrophages

PMID:
29725763
PMCID:
PMC6002457
DOI:
10.1007/s00432-018-2646-0
[Indexed for MEDLINE]
Free PMC Article

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