CD55 is over-expressed in the tumour environment

Abstract

Summary CD55 is a protein that protects cells from complement-mediated attack. 791Tgp72 is an antigen which has been used succesfully as a target for both tumour imaging and cancer vaccines. 791Tgp72 has recently been identified as CD55. Quantitative expression of CD55 in the tumour environment was therefore studied. Tumour cells showed a 4-100-fold increase in CD55 cell surface expression when compared to normal cells. Immunohistochemical staining of colorectal tumours also revealed high expression of CD55 in the stroma. To examine the source of this stromal CD55 the ability of both epithelial cells and endothelial cells to produce extracellular CD55 was measured. Tumour cell lines deposit CD55 into their extracellular matrix (ECM) in direct proportion to their cell surface expression. In contrast the ECM from HUVEC cells contained large amounts of CD55 despite expressing low levels of CD55 on their cell surface. Furthermore expression of CD55 on HUVEC cells was increased by exposure to VEGF. Although it remains unclear why CD55 is upregulated in the tumour environment its high level of expression on tumour cells and associated endothelium may explain why it is a good target for both imaging and immunotherapy. © 2001 Cancer Research Campaign http://www.bjcancer.com Keywords: CD55 (DAF), tumour expression; endothelium; stroma; vascular endothelial growth factor (VEGF) 80Received 27 September 1999 Revised 3 February 2000 Accepted 15 March 2000 Correspondence to : LG Durrant British Journal of Cancer (2001) 84(1), 80-86 © 2001 Cancer Research Campaign doi: 10.1054/ bjoc.2000.1570, available online at http://www.idealibrary.com on http://www.bjcancer.com and tumour-conditioned medium or VEGF (10-300 µg ml -1 : Zeneca, Alderley Park, UK) respectively for 48 h prior to harvesting the HUVECs. Tumour-conditioned media was derived from the MDA 231 breast cancer cell line. These were grown to confluence and the media replaced with serum free M199:Hams F12 medium. Following 24 h incubation the resultant conditioned media was filtered for use with the HUVEC. Fresh media was used to culture the control HUVECs. Freshly resected tumours were finely minced and dissociated in collagenase (0.05%; Boehringer Mannheim) and DNase (0.1%; Boehringer Mannheim) for 1 h at 37˚C. Monoclonal antibodiesMonoclonal antibodies 791T/36 (IgG2b anti-791Tgp72;Embleton et al, 1981), BRIC 216 (IgG1 anti-SCR 3 of CD55; Tate et al, 1989), BRIC 220 (IgG1 anti-SCR 1 of CD55; Tate et al, 1989), BRIC 110 (IgG1 anti-SCR 2 of CD55; Spring et al, 1987;Coyne et al, 1992) have been reported previously. BRIC 229 and E4.3 (Sparrow and Mckenzie, 1983) recognize CD59 and CD46 respectively. The BRIC antibodies were purchased from the Blood Group Reference laboratory (Bristol, UK). Normal mouse IgG (Sigma, Dorset, UK) and 708 monoclonal antibody (IgG2b) was used as negative control antibodies. Indirect immunofluorescenceCell lines were incubated with monoclonal antibody for 1 h at 4˚C. Cells were washed twice in fresh media containing 1% FCS and then incubat...

Characterization of Gene Expression Profiles in Intraductal Papillary-Mucinous Tumors of the Pancreas

“…It has been used successfully as a target for both tumor imaging and cancer vaccines. 35,36 Among the down-regulated genes, we note the presence of several genes implicated in epithelial differentiation as well as in cellular adhesion and maintenance of the cytoskeleton. The low levels of expression of genes implicated in cell cycle regulation (cyclin D2, cdk4) in the IPMTs relative to the HPDE cells probably reflects the fact that the cell line was cultured in logarithmic growth phase, whereas only a limited fraction of cells in any solid tumor is actively proliferating.…”

Prostaglandin E2 Regulates the Complement Inhibitor CD55/Decay-accelerating Factor in Colorectal Cancer

“…These mutually reinforcing effects may further increase production of PGE 2 within the tumor microenvironment, yielding a paracrine loop that mediates increased DAF expression on the surface of tumor cells. Significantly, DAF expression is often much greater on tumor cells than in surrounding normal tissue, particularly in colorectal cancers (19). In addition to providing complement resistance, high levels of DAF can facilitate the dissemination of metastasizing tumor cells once in circulation (8).…”

“…Increased expression of CRPs has been described in several different malignancies, including colorectal (14), gastric (15), lung (16), renal (17), and breast (18) cancers. Specifically, increased DAF expression has been observed in 75% of colorectal cancers compared with matched normal tissue (19), and increased DAF expression has been associated with poor prognosis in patients with colorectal cancer (14). In addition to the angiogenic growth factors such as vascular endothelial growth factor and basic fibroblast growth factor (20), DAF expression is regulated by proinflammatory mediators such as lipopolysaccharide (21), tumor necrosis factor-␣ (22), and IL-1␤ (23).…”

Binding ofEscherichia coliadhesin AfaE to CD55 triggers cell-surface expression of the MHC class I-related molecule MICA

“…However, among the many factors regulating tumor growth, those relevant to MICA expression are still unknown. CD55 expression level is actually increased in a range of tumors and especially colorectal carcinomas (41,42), where it is considered to protect tumor cells from complement attack. With regard to our data, CD55 overexpression in tumors could facilitate adherence of E. coli strains, leading to increased MICA expression and a subsequent MICA-directed immune response.…”