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Macrophages direct tumour histology and clinical outcome in a colon cancer model
Author(s) -
Oosterling Steven J,
van der Bij Gerben J,
Meijer Gerrit A,
Tuk Cornelis W,
van Garderen Evert,
van Rooijen Nico,
Meijer Sybren,
van der Sijp Joost RM,
Beelen Robert HJ,
van Egmond Marjolein
Publication year - 2005
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1830
Subject(s) - cytotoxic t cell , stromal cell , histology , macrophage , pathology , biology , cancer research , cancer cell , malignancy , cancer , stroma , medicine , immunohistochemistry , in vitro , biochemistry , genetics
Macrophages generally constitute a major component of the tumour stroma. Although conventionally considered to be cytotoxic effector cells, macrophages have recently been described as promoters of tumour progression. The present study shows that selective depletion of peritoneal or liver macrophages prior to CC531 tumour cell inoculation resulted in highly differentiated tumours in rats. In contrast, tumours from control rats, in which macrophages are abundantly present, showed a desmoplastic stromal reaction with hallmark features of malignancy, such as neovascularization and matrix remodelling, indicating that the presence of macrophages is associated with malignant histopathological differentiation. Remarkably, macrophage‐depleted rats, bearing highly differentiated tumours, had a worse prognosis, as they displayed a higher tumour load and poorer survival. Thus, while macrophages direct tumours towards malignant tumour histology, their role in anti‐tumour defence is important. The selective inhibition of macrophage functions involved in malignant progression without interfering with cytotoxic ability may therefore identify important new targets for cancer therapy. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.