CFR-1 receptor as target for tumor-specific apoptosis induced by the natural human monoclonal antibody PAM-1.
The human monoclonal antibody PAM-1 was isolated from a patient with stomach cancer. The germ-line coded IgM antibody identifies a recently described 130 kDa variant of CFR-1 (cysteine-rich fibroblast growth factor receptor 1). This CFR-1/PAM-1 receptor is post-transcriptionally modified and over-expressed on human epithelial tumors and carcinoma pre-cancer lesions such as H. pylori induced gastritis, intestinal metaplasia and dysplasia of the stomach, ulcerative colitis-related dysplasia and adenomas of the colon, Barrett metaplasia and dysplasia of the esophagus, squamous cell metaplasia and dysplasia of the lung and cervical intraepithelial neoplasia. Furthermore, the expression of CFR-1/PAM-1 correlates with the proliferation rate and increases with the grade of malignancy. This study demonstrates that the human monoclonal antibody PAM-1 inhibits cell growth and induces apoptosis, in vitro and in vivo. Both, the unique tumor-specific expression of the CFR-1/PAM-1 receptor and the growth inhibitory effect of the PAM-1 antibody makes this combination a good diagnostic and therapeutic tool for all kinds of epithelial cancers and precursor lesions.
Brändlein
Stephanie
S
Institute of Pathology, University Würzburg, D-97080 Würzburg, Germany. path027@mail.uni-wuerzburg.de
Pohle
Tina
T
Vollmers
Christopher
C
Wozniak
Ewa
E
Ruoff
Nele
N
Müller-Hermelink
Hans Konrad
HK
Vollmers
H P
HP
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D001681:Biological Assay; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D007120:Immunochemistry; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D010434:Pepsin A / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000276:immunology; D017468:Receptors, Fibroblast Growth Factor; D012795:Sialoglycoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C493315:PAM-1 monoclonal antibody, human; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D012795:Sialoglycoproteins; C086711:cysteine-rich fibroblast growth factor receptor; D010434:Pepsin A