Expression of acute and late-stage inflammatory antigens, c-fms, CSF-1, and human monocytic serine esterase 1, in tumor-associated macrophages of renal cell carcinomas
B. Hemmerlein et al., Expression of acute and late-stage inflammatory antigens, c-fms, CSF-1, and human monocytic serine esterase 1, in tumor-associated macrophages of renal cell carcinomas, CANCER IMMU, 49(9), 2000, pp. 485-492
Purpose: Tumor cells influence the differentiation of infiltrating macropha
ges. In the present study, the differentiation of macrophages in renal cell
carcinomas was investigated with special regard to their possible role ill
tumor growth and spread. Methods: Macrophages were characterized by means
of immunohistochemistry of the Ki-M1P, 25F9, MRP8, MRP14, and MRP8/14 antig
ens and by means of in situ hybridization of CSF-1, its c-fins-coded corres
ponding receptor, and human monocytic serine esterase-1 (HMSE-1) mRNA. Macr
ophage subgroups were quantified within central tumor tissue, the correspon
ding turner host interface, and tumor-free tissue and correlated with tumor
necrosis, fibrosis, and tumor stage and grade. Results: Macrophage density
was much higher within tumor tissue and the tumor/host interface than in t
umor-free tissue. Well-differentiated carcinomas showed a lower degree of m
acrophage density than less-differentiated carcinomas. Tumor-associated mac
rophages could be divided into an active inflammatory typo (MR14(+), MRP8/1
4(+)) and into a late-phase inflammatory type (25F9(+), MRP8(+)). Necrosis
was seen in less-differentiated carcinomas and associated with a significan
tly increased density of MRP14(+) macrophages, which, however, did not corr
elate with the extent of necrosis. The density of 25F9(+) macrophages was c
orrelated with an extensive connective tissue formation and an advanced tum
or stage. c-fms, CSF-I, and HMSE-1 mRNA expression did not discriminate bet
ween the macrophage subgroups. Conclusions: Tumor-associated macrophages of
the late-stage inflammatory type potentially support the spread of renal c
ell cancer. CSF-1 derived from tumor cells and macrophages acts as a monocy
te attractant and induces macrophage differentiation able to modulate the e
xtracellular matrix rather than to exert cytotoxicity. CSF-1 derived from t
umor cells and macrophages acts as a monocyte attractant and induces macrop
hage differentiation able to modulate the extracellular matrix rather than
to exert cytotoxicity.