ABSTRACT
Decay-accelerating factor (DAF, CD55) is physiologically acting as an inhibitor of the complement system, but is also broadly expressed in malignant tumours. Here DAF seems to exert different functions beyond its immunological role such as e.g. promotion of tumorigenesis, decrease of complement mediated tumor cell lysis, autocrine loops for cell rescue and evasion of apoptosis, neoangiogenesis, invasiveness, cell motility, and metastasis via oncogenic tyrosine kinase pathways and specific seven-span transmembrane receptors (CD97) binding. Therefore, DAF has already become a target for therapy. In this paper we review the role of DAF in human malignancies as described in different basic, diagnostic and experimental therapeutic studies.
Subject(s)
CD55 Antigens/metabolism , Neoplasms/pathology , Neoplasms/therapy , Antigens, CD/metabolism , CD55 Antigens/biosynthesis , CD55 Antigens/chemistry , Humans , Ligands , Membrane Glycoproteins/metabolism , Neoplasms/diagnosis , Phosphotyrosine/metabolism , Receptors, G-Protein-Coupled , Signal TransductionABSTRACT
By differential-display PCR a subclone of the SKBR3 cell line with high in vitro transendothelial invasiveness was identified to express increased levels of the INSL-4 gene. This new member of the insulin-like growth factor family encodes for a peptide, designated early placenta insulin-like (EPIL), being expressed in the so-called "invasive" phase of the placental development. Immunohistochemistry on tissue microarrays revealed a heterogeneous expression of EPIL in breast cancer tissue and no expression in the surrounding stroma cells. A coexpression of pro-EPIL and c-erbB-2 could be observed predominantly in cell clusters at the infiltrating edge of the tumor. Our results give new suggestions for the presence of a signaling network of receptor tyrosine kinases underlying breast cancer invasion and metastasis.
