Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms
2015 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 6, no 11, 9045-9060 p.Article in journal (Refereed) Published
Podoplanin (PDPN) is a unique transmembrane receptor that promotes tumor cell motility. Indeed, PDPN may serve as a chemotherapeutic target for primary and metastatic cancer cells, particularly oral squamous cell carcinoma (OSCC) cells that cause most oral cancers. Here, we studied how a monoclonal antibody (NZ-1) and lectin (MASL) that target PDPN affect human OSCC cell motility and viability. Both reagents inhibited the migration of PDPN expressing OSCC cells at nanomolar concentrations before inhibiting cell viability at micromolar concentrations. In addition, both reagents induced mitochondrial membrane permeability transition to kill OSCC cells that express PDPN by caspase independent nonapoptotic necrosis. Furthermore, MASL displayed a surprisingly robust ability to target PDPN on OSCC cells within minutes of exposure, and significantly inhibited human OSCC dissemination in zebrafish embryos. Moreover, we report that human OSCC cells formed tumors that expressed PDPN in mice, and induced PDPN expression in infiltrating host murine cancer associated fibroblasts. Taken together, these data suggest that antibodies and lectins may be utilized to combat OSCC and other cancers that express PDPN.
Place, publisher, year, edition, pages
IMPACT JOURNALS LLC , 2015. Vol. 6, no 11, 9045-9060 p.
podoplanin; cancer; cell migration; receptor; lectin
Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:liu:diva-120753ISI: 000358774600044PubMedID: 25826087OAI: oai:DiVA.org:liu-120753DiVA: diva2:848169
Funding Agencies|Osteopathic Heritage Foundation; Northarvest Bean Growers Association; New Jersey Health Foundation; Sentrimed; Platform for Drug Discovery, Informatics, and Structural Life Science from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan; Regional Innovation Strategy Support Program from MEXT of Japan; MEXT of Japan2015-08-242015-08-242016-04-24