Tumor-associated macrophages in clear cell renal cell carcinoma express both gastrin-releasing peptide and its receptor: a possible modulatory role of immune effectors cells.
OBJECTIVE
Renal cell carcinomas (RCC) frequently express the gastrin-releasing peptide receptor (GRP-R). Gastrin-releasing peptide (GRP) stimulates tumor cell proliferation and neoangiogenesis. Tumor-associated macrophages (TAM) comprise an important cellular component of these tumors. We analyzed the GRP/GRP-R network in clear cell RCC (ccRCC) and non-clear cell RCC (non-ccRCC) with special regard to its expression by macrophages, tumor cells and microvessels.


METHODS
Gastrin-releasing peptide and GRP-R expression in 17 ccRCC and 9 non-ccRCC were analyzed by RT-PCR, immunohistochemistry and double immunofluorescence staining.


RESULTS
Tumor-associated macrophages expressed GRP and GRP receptor in ccRCC. Tumor cells and microvessels showed low to intermediate GRP-R expression in nearly all cases. In 12 ccRCC tumor epithelia also expressed low levels of GRP. Microvascular GRP expression was found in nine cases of ccRCC. For non-RCC, the expression of GRP and GRP receptor expression pattern was similar.


CONCLUSIONS
Tumor-associated macrophages are the main source of GRP in RCC. GRP receptor on TAM, tumor epithelia and microvessels might be a molecular base of a GRP/GRP receptor network, potentially acting as a paracrine/autocrine modulator of TAM recruitment, tumor growth and neoangiogenesis.
Bedke
Jens
J
Department of Urology, Eberhard Karls University of Tübingen, Tübingen, Germany.
Hemmerlein
Bernhard
B
Perske
Christina
C
Gross
Andreas
A
Heuser
Markus
M
D000368:Aged; D000704:Analysis of Variance; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D015331:Cohort Studies; D005260:Female; D005455:Fluorescent Antibody Technique; D019886:Gastrin-Releasing Peptide / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018004:Receptors, Bombesin / Q000378:metabolism*; D012016:Reference Values; D012680:Sensitivity and Specificity
D018004:Receptors, Bombesin; D019886:Gastrin-Releasing Peptide