Analysis of CC chemokine and chemokine receptor expression in solid ovarian tumours.
To understand the chemokine network in a tissue, both chemokine and chemokine receptor expression should be studied. Human epithelial ovarian tumours express a range of chemokines but little is known about the expression and localisation of chemokine receptors. With the aim of understanding chemokine action in this cancer, we investigated receptors for CC-chemokines and their ligands in 25 biopsies of human ovarian cancer. CC-chemokine receptor mRNA was generally absent from solid tumours, the exception being CCR1 which was detected in samples from 75% of patients. CCR1 mRNA localised to macrophages and lymphocytes and there was a correlation between numbers of CD8(+) and CCR1 expressing cells (P = 0.031). mRNA for 6 CC-chemokines was expressed in a majority of tumour samples. In a monocytic cell line in vitro, we found that CCR1 mRNA expression was increased 5-fold by hypoxia. We suggest that the CC-chemokine network in ovarian cancer is controlled at the level of CC-chemokine receptors and this may account for the phenotypes of infiltrating cells found in these tumours. The leukocyte infiltrate may contribute to tumour growth and spread by providing growth survival factors and matrix metalloproteases. Thus, CCR1 may be a novel therapeutic target in ovarian cancer.
Scotton
C
C
ICRF Translational Oncology Laboratory, St Bartholomew's and Royal London School of Medicine and Dentistry, Science Building, Charterhouse Square, London EC1M 6BQ, UK.
Milliken
D
D
Wilson
J
J
Raju
S
S
Balkwill
F
F
D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D015152:Blotting, Northern; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019742:Chemokines, CC / Q000235:genetics* / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012260:Ribonucleases / Q000378:metabolism
C515300:CCR1 protein, human; D019742:Chemokines, CC; D012333:RNA, Messenger; D054389:Receptors, CCR1; D019707:Receptors, Chemokine; D012260:Ribonucleases