Targeting CUB domain-containing protein 1 with a monoclonal antibody inhibits metastasis in a prostate cancer model.
Through a whole-cell panning approach, we previously identified a panel of antibodies that bound to prostate cancer cell surface antigens. One such antigen, CUB domain-containing protein 1 (CDCP1), was recognized by monoclonal antibody 25A11 and is a single transmembrane molecule highly expressed in several metastatic cancers as well as on CD34(+)CD133(+) myeloid leukemic blast cells. We show CDCP1 expression on prostate cancer cell lines by real-time quantitative PCR (RT-qPCR), flow cytometry, and immunohistochemistry and on prostate cancer patient samples by RT-qPCR and immunohistochemical staining. In cell-based assays, antibody 25A11 inhibited prostate cancer cell migration and invasion in vitro. Further characterization showed that CDCP1 is internalized on antibody binding. When 25A11 was coupled to the cytotoxin saporin either directly or via a secondary antibody, both resulted in prostate cancer cell killing in vitro. In vivo targeting studies with an anti-CDCP1 immunotoxin showed significant inhibition of primary tumor growth as well as metastasis in a mouse xenograft model. These data provide support for continued evaluation of anti-CDCP1 therapy for potential use in cancer in primary and metastatic disease.
Siva
Amara C
AC
Alexion Antibody Technologies, Inc., San Diego, California, USA.
Wild
Martha A
MA
Kirkland
Richard E
RE
Nolan
Mary Jean
MJ
Lin
Bing
B
Maruyama
Toshiaki
T
Yantiri-Wernimont
Ferda
F
Frederickson
Shana
S
Bowdish
Katherine S
KS
Xin
Hong
H
D000071916:AC133 Antigen; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D015703:Antigens, CD / Q000096:biosynthesis / Q000737:chemistry* / Q000502:physiology; D018952:Antigens, CD34 / Q000096:biosynthesis; D000951:Antigens, Neoplasm / Q000737:chemistry* / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000502:physiology; D002465:Cell Movement; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000502:physiology; D009368:Neoplasm Transplantation; D010455:Peptides; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D017434:Protein Structure, Tertiary
D000071916:AC133 Antigen; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018952:Antigens, CD34; D000951:Antigens, Neoplasm; C432044:CDCP1 protein, human; C529673:CDCP1 protein, mouse; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse