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Tumor‐promoting macrophages induce the expression of the macrophage‐specific receptor CD163 in malignant cells
Author(s) -
Maniecki Maciej Bogdan,
Etzerodt Anders,
Ulhøi Benedicte Parm,
Steiniche Torben,
Borre Michael,
Dyrskjøt Lars,
Ørntoft Torben Falck,
Moestrup Søren Kragh,
Møller Holger Jon
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27506
Subject(s) - cd163 , bladder cancer , pathology , cd68 , metastasis , malignancy , cancer research , cancer cell , medicine , immunostaining , cancer , tumor progression , tumor microenvironment , biology , macrophage , immunohistochemistry , in vitro , biochemistry
Tumor‐associated macrophages (TAMs) represent a distinct malignancy‐promoting phenotype suggested to play a key role in tumor formation and metastasis. We aimed to investigate the expression of the monocyte/macrophage‐restricted receptor CD163 in bladder tumor biopsies and assess the potential mechanism inducing the CD163 expression in tumor cells. A high CD163 mRNA expression ( n = 87) was significantly associated with a poor 13‐year overall survival (log‐rank test, χ 2 = 8.931; p = 0.0028). Moreover, CD163 mRNA expression was significantly increased in muscle invasive (T2–T4), p = 0.017, and aggressive (grade III/IV) cancers ( p = 0.015). The expression strongly correlated with local expression of IL‐6 ( r = 0.72; p <0.0001) and IL‐10 ( r = 0.75; p <0.0001), mediators known to induce CD163 expression in vitro . CD163 immunostaining ( n = 46) confirmed the association between dense TAM infiltration and histologically advanced disease. In 39% of the biopsies, CD163 immunoreactivity was also observed in tumor cells, and CD163‐expressing metastatic cells were identified in lymph node biopsies ( n = 8). Bladder cancer cell lines did not express CD163; however, when cocultured with macrophages the bladder cancer cell expression of CD163 was significantly induced in an IL‐6/IL‐10 independent manner. In conclusion, we show a strong association between CD163 mRNA expression in bladder cancer biopsies and poor patient outcome. CD163 expression was not confined to the infiltrating TAMs, but was also expressed by a significant portion of the malignant cells in both tumors and lymph nodes. CD163 expressing tumor cells may constitute a subpopulation of tumor cells with a phenotypic shift associated with epithelial‐to‐mesenchymal transition (EMT) and increased metastatic activity induced by TAMs.