Immunohistochemical identification of complement peptide C5a receptor 1 (C5aR1) in non-neoplastic and neoplastic human tissues.

Abstract

The complement component C5a and its receptor C5aR1 are involved in the development of numerous inflammatory diseases. In addition to immune cells, C5aR1 is expressed in neoplastic cells of multiple tumour entities, where C5aR1 is associated with a higher proliferation rate, advanced tumour stage, and poor patient outcomes. The aim of the present study was to obtain a broad expression profile of C5aR1 in human non-neoplastic and neoplastic tissues, especially in tumour entities not investigated in this respect so far. For this purpose, we generated a novel polyclonal rabbit antibody, {5227}, against the carboxy-terminal tail of C5aR1. The antibody was initially characterised in Western blot analyses and immunocytochemistry using transfected human embryonic kidney (HEK) 293 cells. It was then applied to a large series of formalin-fixed, paraffin-embedded non-neoplastic and neoplastic human tissue samples. C5aR1 was strongly expressed by different types of immune cells in the majority of tissue samples investigated. C5aR1 was also present in alveolar macrophages, bronchial, gut, and bile duct epithelia, Kupffer cells, occasionally in hepatocytes, proximal renal tubule cells, placental syncytiotrophoblasts, and distinct stem cell populations of bone marrow. C5aR1 was also highly expressed in the vast majority of the 32 tumour entities investigated, where a hitherto unappreciated high prevalence of the receptor was detected in thyroid carcinomas, small-cell lung cancer, gastrointestinal stromal tumours, and endometrial carcinomas. In addition to confirming published findings, we found noticeable C5aR1 expression in many tumour entities for the first time. Here, it may serve as an interesting target for future therapies.