EpCAM (CD326) finding its role in cancer

Although epithelial cell adhesion/activating molecule (EpCAM/CD326) is one of the first tumour-associated antigens identified, it has never received the same level of attention as other target proteins for therapy of cancer. It is also striking that ever since its discovery in the late 1970s the actual contribution of EpCAM to carcinogenesis remained unexplored until very recently. With a First International Symposium on EpCAM Biology and Clinical Application this is now changing. Key topics discussed at the meeting were the frequency and level of EpCAM expression on various cancers and its prognostic potential, the role of EpCAM as an oncogenic signalling molecule for cancer cells, recent progress on EpCAM-directed immunotherapeutic approaches in clinical development and the interaction of EpCAM with other proteins, which may provide a basis for a therapeutic window and repression of its growth-promoting signalling in carcinoma. Future research on EpCAM may benefit from a unified nomenclature and more frequent exchange among those who have been working on this cancer target during the past 30 years and will do so in the future.

[1]  B. Wollenberg,et al.  Tumor-specific glycosylation of the carcinoma-associated epithelial cell adhesion molecule EpCAM in head and neck carcinomas. , 2003, Cancer letters.

[2]  G. Sauter,et al.  High Ep-CAM Expression is Associated with Poor Prognosis in Node-positive Breast Cancer , 2004, Breast Cancer Research and Treatment.

[3]  S. Braun,et al.  The persistence of isolated tumor cells in bone marrow from patients with breast carcinoma predicts an increased risk for recurrence , 2005, Cancer.

[4]  Thomas Rau,et al.  Circulating Tumor Cells in Breast Cancer: Correlation to Bone Marrow Micrometastases, Heterogeneous Response to Systemic Therapy and Low Proliferative Activity , 2005, Clinical Cancer Research.

[5]  D. Speicher,et al.  Sequence investigation of the major gastrointestinal tumor-associated antigen gene family, GA733. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[6]  P. Kufer,et al.  In vitro and in vivo activity of MT201, a fully human monoclonal antibody for pancarcinoma treatment , 2002, International journal of cancer.

[7]  A. Luebke,et al.  Ep-CAM expression in squamous cell carcinoma of the esophagus: a potential therapeutic target and prognostic marker , 2006, BMC Cancer.

[8]  R. Kimmig,et al.  MT110: a novel bispecific single-chain antibody construct with high efficacy in eradicating established tumors. , 2006, Molecular immunology.

[9]  J. M. Chong,et al.  Determination of Disulfide Bond Assignments andN-Glycosylation Sites of the Human Gastrointestinal Carcinoma Antigen GA733-2 (CO17-1A, EGP, KS1-4, KSA, and Ep-CAM)* , 2001, The Journal of Biological Chemistry.

[10]  G. Schlimok,et al.  Combination of high-dose chemotherapy and monoclonal antibody in breast-cancer patients: a pilot trial to monitor treatment effects on disseminated tumor cells. , 2000, Cytotherapy.

[11]  Markus Münz,et al.  The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation , 2004, Oncogene.

[12]  G. Riethmüller,et al.  The epithelial cell surface antigen 17–1A, a target for antibody‐mediated tumor therapy: Its biochemical nature, tissue distribution and recognition by different monoclonal antibodies , 1986, International journal of cancer.

[13]  N. Katunuma,et al.  Involvement of cathepsins in the invasion, metastasis and proliferation of cancer cells. , 2005, The journal of medical investigation : JMI.

[14]  W. Parson,et al.  Methylation status of the Ep-CAM promoter region in human breast cancer cell lines and breast cancer tissue. , 2007, Cancer letters.

[15]  H. Moch,et al.  Overexpression of epithelial cell adhesion molecule (Ep-CAM) is an independent prognostic marker for reduced survival of patients with epithelial ovarian cancer. , 2006, Gynecologic oncology.

[16]  Y. Hannun,et al.  EpCAM Is Overexpressed in Breast Cancer and Is a Potential Target for Breast Cancer Gene Therapy , 2004, Cancer Research.

[17]  I. Kawase,et al.  CD9 overexpression suppressed the liver metastasis and malignant ascites via inhibition of proliferation and motility of small-cell lung cancer cells in NK cell-depleted SCID mice. , 2005, Oncology research.

[18]  M. Steurer,et al.  Ep-CAM expression in pancreatic and ampullary carcinomas: frequency and prognostic relevance , 2006, Journal of Clinical Pathology.

[19]  C. Punt,et al.  Edrecolomab alone or in combination with fluorouracil and folinic acid in the adjuvant treatment of stage III colon cancer: a randomised study , 2002, The Lancet.

[20]  P. Hersey,et al.  Expression of the neuroglandular antigen and analogues in melanoma. CD9 expression appears inversely related to metastatic potential of melanoma , 1993, International journal of cancer.

[21]  G. Schäfer,et al.  Overexpression of Epithelial Cell Adhesion Molecule Antigen in Gallbladder Carcinoma Is an Independent Marker for Poor Survival , 2004, Clinical Cancer Research.

[22]  N. Stoecklein,et al.  Genetic heterogeneity of single disseminated tumour cells in minimal residual cancer , 2002, The Lancet.

[23]  M C Miller,et al.  Expression of epithelial cell adhesion molecule in carcinoma cells present in blood and primary and metastatic tumors. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  Rudolf M. Huber,et al.  Combined transcriptome and genome analysis of single micrometastatic cells , 2002, Nature Biotechnology.

[25]  J. Witte,et al.  Monoclonal antibody therapy for resected Dukes' C colorectal cancer: seven-year outcome of a multicenter randomized trial. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  K. Pantel,et al.  BM micrometastases and circulating tumor cells in breast cancer patients: where have we been, where are we now and where does the future lie? , 2005, Cytotherapy.

[27]  H. Moch,et al.  Expression of Epithelial Cell Adhesion Molecule (EpCam) in Renal Epithelial Tumors , 2005, The American journal of surgical pathology.

[28]  S. Itoi,et al.  Motility-related protein-1 (MRP-1/CD9) reduction as a factor of poor prognosis in breast cancer. , 1996, Cancer research.

[29]  K. Pantel,et al.  Detection and molecular characterisation of disseminated tumour cells: implications for anti-cancer therapy. , 2005, Biochimica et biophysica acta.

[30]  Marko Novinec,et al.  Diversity and evolution of the thyroglobulin type-1 domain superfamily. , 2006, Molecular biology and evolution.

[31]  S. Morrison,et al.  Prospective identification of tumorigenic breast cancer cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[32]  H. A. Bakker,et al.  Evidence for a role of the epithelial glycoprotein 40 (Ep-CAM) in epithelial cell-cell adhesion. , 1994, Cell adhesion and communication.

[33]  Falk Schubert,et al.  Bi-specific immunomagnetic enrichment of micrometastatic tumour cell clusters from bone marrow of cancer patients. , 2005, Journal of immunological methods.

[34]  G. Riethmüller,et al.  Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma , 1994, The Lancet.

[35]  M Vasei,et al.  Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers , 2006, British Journal of Cancer.

[36]  L. Hültner,et al.  Bispecific antibodies target operationally tumor-specific antigens in two leukemia relapse models. , 1996, Blood.

[37]  H. Koprowski,et al.  Effects of monoclonal antibody immunotherapy on patients with gastrointestinal adenocarcinoma. , 1984, Journal of biological response modifiers.

[38]  H. Koprowski,et al.  PHASE-I CLINICAL TRIAL OF MONOCLONAL ANTIBODY IN TREATMENT OF GASTROINTESTINAL TUMOURS , 1982, The Lancet.

[39]  T. Fehm,et al.  A pooled analysis of bone marrow micrometastasis in breast cancer. , 2005, The New England journal of medicine.

[40]  A. Kopp-Schneider,et al.  Adjuvant Therapy with Edrecolomab versus Observation in Stage II Colon Cancer: A Multicenter Randomized Phase III Study* , 2005, Oncology Research and Treatment.

[41]  Alessandro Lugli,et al.  Frequent EpCam protein expression in human carcinomas. , 2004, Human pathology.

[42]  M. Herlyn,et al.  Colorectal carcinoma-specific antigen: detection by means of monoclonal antibodies. , 1979, Proceedings of the National Academy of Sciences of the United States of America.