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Stem cell marker-positive stellate cells and mast cells are reduced in benign-appearing bladder tissue in patients with urothelial carcinoma

Abstract

Survival after invasive bladder cancer has improved less than that of other common non-skin cancers. In many types of malignancy, treatment failure has been attributed to therapy-resistant stem-like cancer cells. Our aim was therefore to determine identities of stem cell marker-positive cells in bladder cancer tissue and to investigate possible associations between these cells and different forms of bladder neoplasia. We investigated tissue from 52 patients with bladder neoplasia and 18 patients with benign bladder conditions, from a cohort that had been previously described with regard to diagnosis and outcome. The samples were analysed immunohistologically for the stem cell markers aldehyde dehydrogenase 1 A1 (ALDH1) and CD44, and markers of cell differentiation. The majority of stem cell marker-positive cells were located in connective tissue, and a smaller fraction in epithelial tissue. Stem cell marker-positive cells exhibiting possible stem cell characteristics included cells in deeper locations of benign and malignant epithelium, and sub-endothelial cells in patients with or without neoplasia. Stem cell marker-positive cells with non-stem cell character included stellate cells, mast cells, endothelial cells, foamy histiocytes, and neurons. Significantly, ALDH1+ stellate cells and ALDH1+ mast cells were reduced in number in stroma of benign-appearing mucosa of bladder cancer patients. The stem cell markers ALDH1 and CD44 label several types of differentiated cells in bladder tissue. ALDH1+ stellate cells and mast cells appear to be reduced in stroma of normal-appearing mucosa of bladder cancer patients, and may be part of a “field effect” in cancer-near areas.

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Acknowledgments

This study was financed by the Telemark Hospital Research and Development Fund. We thank Linda Røland Svensson at Telemark Hospital and Ulla Larsson Petterson at Akademiska Sjukhuset Uppsala for laboratory assistance, and ImaGene-iT AB in Sweden for image processing and figure compilation.

Acknowledgment of funding and grants

R&D Fund, Telemark Hospital, 3710 Skien, Norway

Disclosure of Conflict of Interest

The authors declare that they have no conflict of interest.

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Correspondence to Björn L. Isfoss.

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Isfoss, B.L., Busch, C., Hermelin, H. et al. Stem cell marker-positive stellate cells and mast cells are reduced in benign-appearing bladder tissue in patients with urothelial carcinoma. Virchows Arch 464, 473–488 (2014). https://doi.org/10.1007/s00428-014-1561-2

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Keywords

  • Bladder cancer
  • Tumour microenvironment
  • Stem cells
  • Stellate cells
  • Mast cells
  • Aldehyde dehydrogenase
  • CD44