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Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms.

Ochoa-Alvarez JA, Krishnan H, Pastorino JG, Nevel E, Kephart D, Lee JJ, Retzbach EP, Shen Y, Fatahzadeh M, Baredes S, Kalyoussef E, Honma M, Adelson ME, Kaneko MK, Kato Y, Young MA, Deluca-Rapone L, Shienbaum AJ, Yin K, Jensen LD, Goldberg GS - Oncotarget (2015)

Bottom Line: 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.Taken together, these data suggest that antibodies and lectins may be utilized to combat OSCC and other cancers that express PDPN.

View Article: PubMed Central - PubMed

Affiliation: Departments of Molecular Biology, Cell Biology, and Pathology, School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

PDPN expression in human OSCC cells and infiltrating mouse fibroblasts in xenograft tumorsTumors from HSC-2 cells were examined with antisera specific for human (D2-40) and mouse (8.1.1) PDPN by immunohistochemistry as indicated.
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Figure 10: PDPN expression in human OSCC cells and infiltrating mouse fibroblasts in xenograft tumorsTumors from HSC-2 cells were examined with antisera specific for human (D2-40) and mouse (8.1.1) PDPN by immunohistochemistry as indicated.

Mentions: In addition to cancer cells themselves, PDPN expression in cancer associated fibroblasts has been associated with tumor aggression and poor clinical outcomes [85]. This has been found in a variety of cancers including mammary carcinoma [86, 87], melanoma [88], lung squamous cell carcinoma [89], esophageal adenocarcinoma [90], and OSCC [91]. Interestingly, human HSC-2 cells form tumors that express PDPN in mice, and also induce PDPN expression in infiltrating mouse cancer associate fibroblasts within the stroma of the tumor as shown in Figure 10. These data are consistent with recent findings that cancer associated fibroblasts express PDPN to promote the motility and survival of neighboring tumor cells [72].


Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms.

Ochoa-Alvarez JA, Krishnan H, Pastorino JG, Nevel E, Kephart D, Lee JJ, Retzbach EP, Shen Y, Fatahzadeh M, Baredes S, Kalyoussef E, Honma M, Adelson ME, Kaneko MK, Kato Y, Young MA, Deluca-Rapone L, Shienbaum AJ, Yin K, Jensen LD, Goldberg GS - Oncotarget (2015)

PDPN expression in human OSCC cells and infiltrating mouse fibroblasts in xenograft tumorsTumors from HSC-2 cells were examined with antisera specific for human (D2-40) and mouse (8.1.1) PDPN by immunohistochemistry as indicated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496201&req=5

Figure 10: PDPN expression in human OSCC cells and infiltrating mouse fibroblasts in xenograft tumorsTumors from HSC-2 cells were examined with antisera specific for human (D2-40) and mouse (8.1.1) PDPN by immunohistochemistry as indicated.
Mentions: In addition to cancer cells themselves, PDPN expression in cancer associated fibroblasts has been associated with tumor aggression and poor clinical outcomes [85]. This has been found in a variety of cancers including mammary carcinoma [86, 87], melanoma [88], lung squamous cell carcinoma [89], esophageal adenocarcinoma [90], and OSCC [91]. Interestingly, human HSC-2 cells form tumors that express PDPN in mice, and also induce PDPN expression in infiltrating mouse cancer associate fibroblasts within the stroma of the tumor as shown in Figure 10. These data are consistent with recent findings that cancer associated fibroblasts express PDPN to promote the motility and survival of neighboring tumor cells [72].

Bottom Line: 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.Taken together, these data suggest that antibodies and lectins may be utilized to combat OSCC and other cancers that express PDPN.

View Article: PubMed Central - PubMed

Affiliation: Departments of Molecular Biology, Cell Biology, and Pathology, School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus