title: Widespread expressions of immunoglobulin superfamily proteins in cancer cells.
abstract: RP215 monoclonal antibody (Mab) was shown to recognize a carbohydrate-associated epitope of cancer cell-expressed glycoproteins, known as CA215. Extensive MALDI-TOF MS analysis was performed to search for the molecular identity of CA215. Besides immunoglobulin (Ig) heavy chains, homology to human T-cell receptors (TCR) and Ig-like cell adhesion molecules was also detected. By using RT-PCR and cDNA sequencing, it was observed that as many as 80% of cancer cell lines showed significant levels of gene expressions of TCR-α and TCR-β. Selected Ig-like cell adhesion molecules such as CD47, CD54, CD58 and CD 147 were also highly expressed among all the cell lines tested. In contrast, co-receptors and co-stimulators of TCR such as CD3, CD4 and CD8 were rarely expressed demonstrating the non-functional nature of TCR in cancer cells. Results of immunohistochemical staining and Western blot assays of cancer cell lines as well as cancerous tissue sections were consistent with these observations. Anti-TCR and anti-human IgG antibodies were shown to induce complement-dependent cytotoxicity and apoptosis of cultured cancer cells indicating the surface nature of Ig-like proteins. Based on these experimental observations, it was hypothesized that the expressions of these immunoglobulin superfamily (IgSF) proteins may be relevant to the immune protection and proliferations of cancer cells during carcinogenesis or cancer progression. Surface-bound TCR-like proteins as well as immunoglobulins may be the potential targets for RP215-based anti-cancer drugs.
authors.affiliation: Andrology Laboratory, UBC Centre for Reproductive Health, The University of British Columbia, 4500 Oak Street, Vancouver, BC V6H 3N1, Canada. cyglee@yahoo.com
authors.forename: Gregory
authors.initials: G
authors.lastname: Lee
authors.forename: Mingang
authors.initials: M
authors.lastname: Zhu
authors.forename: Bixia
authors.initials: B
authors.lastname: Ge
authors.forename: Suzanne
authors.initials: S
authors.lastname: Potzold
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D018394:CA-125 Antigen / Q000737:chemistry / Q000276:immunology; D045744:Cell Line, Tumor; D045325:HCT116 Cells; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000737:chemistry / Q000276:immunology; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: D000911:Antibodies, Monoclonal; D018394:CA-125 Antigen; D007136:Immunoglobulins; C451759:MUC16 protein, human; D008565:Membrane Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger