CD97 is an EGF-TM7 receptor found on various carcinomas where expression levels correlate with dedifferentiation and tumor stage, smooth muscle cells and leukocytes. CD97 acts as an adhesion molecule by binding to its cellular ligand, CD55. In this study, we demonstrate that 2 immunodominant CD97 epitopes are not equally present in the various cell types. Differences were apparent in gastrointestinal tumors and smooth muscle cells where monoclonal antibodies (mAbs) to the first epidermal growth factor (EGF) domain (CD97 EGF ) showed a more restricted staining pattern than mAbs to the stalk region (CD97 stalk ). This discrepancy was not detectable in cultured gastrointestinal tumor cell lines. In fact, the selection of the CD97 mAb influences the result of clinical studies. Thus, we clarified the reason(s) for these differences in CD97 mAb staining on various cell types. We provide evidence that epitope accessibility for CD97 EGF Key words: CD97; colorectal cancer; smooth muscle cell; epitope accessibility; glycosylation CD97 is a member of a subfamily of 7-span transmembrane (TM7) receptors referred to as EGF-TM7 proteins. 1,2 In normal tissues, CD97 is abundantly expressed in smooth muscle cells, macrophages, granulocytes, dendritic cells and in some T and B cells. 3 Carcinomas of different origin showed higher CD97 expression compared to the corresponding normal cell types. 4 -7 CD97 consists of an extended extracellular region with several N-terminal epidermal growth factor (EGF) domains coupled to the TM7 domain by a stalk. 1,8 Various CD97 isoforms exist possessing 3 (EGF 1,2,5), 4 (EGF 1,2,3,5), or 5 (EGF 1,2,3,4,5) EGF domains. CD97 binds to membrane receptor CD55. 9 This interaction is mediated by the first 2 CD97 EGF domains. 9 -11 Chondroitin sulfate glycosaminoglycan, present in cell membranes and the extracellular matrix, is a new ligand to the longest CD97 isoform (EGF 1,2,3,4,5). 12 The ability of CD97 EGF domains to interact with cellular and/or extracellular matrix ligands suggests that the molecule is involved in cell-cell or cell-matrix interactions. Various lines of evidence have shown an important role for CD97 in tumor dedifferentiation, migration, invasiveness and metastasis. CD97 levels correlate with the in vitro migration and invasion capacity of colorectal tumor cell lines and CD97-transfected cells. 6 Colorectal carcinomas with more strongly CD97-stained, scattered tumor cells at the invasion front showed a poorer clinical stage as well as increased lymph vessel invasion compared to cases with uniform CD97 staining. 6 In thyroid cancers, CD97 expression parallels the aggressiveness and lymph node involvement of these tumors. 4,5 Our previous data revealed that CD97 has prognostic and therapeutic potential in cancer. However, analyzing CD97 expression brings up the phenomenon that different staining patterns, depending on which CD97 monoclonal antibody (mAb) has been used for immunohistology, can be readily observed in pancreatic tissues. 7,13 Based on this observation, one aim of ...

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Abstract. Cytochrome P450 1A1 (CYP1A1) belongs to the enzymes of biotransformation of phase I. CYP1A1 performs the catalytic activation of exogenous and endogenous substrates to more carcinogenic metabolites. Overexpression of the wild-type and a recently described splice variant (CYP1A1v, ovarian cancer) are attributed to neoplastic transformation. Here we describe novel CYP1A1 splicing variants commonly and frequently transcribed in leucocytes of healthy volunteers, separated from variants exclusively expressed in tumour cell lines. Interestingly, all the novel splicing variants in leukocytes are generated by employing of two nested splice site pairs, one outer canonical and one inner non-canonical splice site pair, within the exon 2 of the human CYP1A1. In general, the frequent presence of common splicing variants in healthy volunteers has to be consider as a physiological feature of human CYP1A1 transcription process, rather than a signature of carcinogenesis.

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