CXC chemokines modulate host immunity, neovascularization, growth and invasive behaviour of tumours. Despite their relevance in tumour biology,
chemokine expression in intestinal- and diffuse-type gastric
carcinoma, which exhibit a completely different growth pattern, has not been investigated in detail. In this study, expression of the
CXC chemokines CXCL8 [
interleukin (IL)-8], CXCL1 [growth-related oncogene alpha (Gro alpha)], CXCL9 [monokine induced by
interferon (IFN)-gamma] and CXCL10 [IFN-gamma-inducible protein-10 (IP-10)] and the corresponding
chemokine receptors CXCR1-3 was investigated by immunohistochemistry in intestinal- and diffuse-type gastric
carcinoma. Tumour cells of all patients expressed CXCL8. CXCL8 expression was significantly stronger in tumour cells of diffuse- rather than intestinal-type gastric
carcinoma (P < 0.01) as determined by a semiquantitative score. CXCL1 was expressed almost exclusively by diffuse- but not intestinal-type
carcinoma cells. The corresponding
chemokine receptors, CXCR1 and CXCR2, were found on
carcinoma cells. Furthermore, CXCL8 expression correlated with number of tumour vessels (P < 0.01), suggesting an angiogenetic function in gastric
carcinoma not only in vitro but also in vivo. CXCL10 and CXCL9, attractants for T cells, were expressed by peritumorous macrophages in close proximity to IFN-gamma-producing CXCR3-positive T cells in both tumour types. These
chemokines may attract gastric
carcinoma-infiltrating T cells via an IFN-gamma-mediated pathway and enhance host immunity against the tumour. In gastric
carcinoma a complex interplay between
CXC-chemokine signals derived from both tumour cells and tumour-infiltrating immune cells may exhibit pleiotropic effects in tumour biology that go far beyond their originally described functions as leucocyte
chemoattractants. Because CXCL8 and CXCL1, which are known to increase growth and invasive behaviour of malignant tumours, are significantly stronger expressed in diffuse- than intestinal-type gastric
carcinoma, one may speculate that these
chemokines influence the different growth pattern of gastric
carcinoma types.