Inhibition of experimental metastasis by targeting the HUIV26 cryptic epitope in collagen.
Metastasis from the primary tumor to distant sites involves an array of molecules that function in an integrated manner. Proteolytic remodeling and subsequent tumor cell interactions with the extracellular matrix regulate tumor invasion. In previous studies, we have identified a cryptic epitope (HUIV26) that is specifically exposed after alterations in the triple helical structure of type IV collagen. Exposure of this cryptic epitope plays a fundamental role in the regulation of angiogenesis in vivo. However, little is known concerning the ability of tumor cells to interact with this cryptic site or whether this site regulates tumor cell metastasis in vivo. In this regard, many of the same cellular processes that regulate angiogenesis also contribute to tumor metastasis. Here we provide evidence that tumor cells such as B16F10 melanoma interact with denatured collagen type IV in part by recognizing the HUIV26 cryptic site. Systemic administration of a HUIV26 monoclonal antibody inhibited experimental metastasis of B16F10 melanoma in vivo. Taken together, our findings suggest that tumor cell interactions with the HUIV26 cryptic epitope play an important role in regulating experimental metastasis and that this cryptic element may represent a therapeutic target for controlling the spread of tumor cells to distant sites.
Roth
Jennifer M
JM
Department of Radiation Oncology, The New York University Cancer Institute, New York University School of Medicine, New York 10016, USA.
Caunt
Maresa
M
Cretu
Alexandra
A
Akalu
Abebe
A
Policarpio
Desiree
D
Li
Xiaolu
X
Gagne
Paul
P
Formenti
Silvia
S
Brooks
Peter C
PC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo; D003094:Collagen / Q000737:chemistry* / Q000276:immunology*; D024141:Collagen Type IV / Q000737:chemistry; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000939:Epitopes / Q000276:immunology*; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary*; D051379:Mice; D009362:Neoplasm Metastasis / Q000235:genetics / Q000276:immunology* / Q000628:therapy
D000911:Antibodies, Monoclonal; D024141:Collagen Type IV; D000939:Epitopes; D003094:Collagen