Oncotarget: Inhibit oral squamous carcinoma cell migration and viability

Here is a link to a video interview with Dr. Gary S. Goldberg about this research on the Oncotarget Research Paper

Oncotarget published "Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms" which reported that Indeed, PDPN may serve as a chemotherapeutic target for primary and metastatic cancer cells, particularly oral squamous cell carcinoma cells that cause most oral cancers.

Both reagents inhibited the migration of PDPN expressing OSCC cells at nanomolar concentrations before inhibiting cell viability at micromolar concentrations.

In addition, both reagents induce 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, the Oncotarget authors report that human OSCC cells formed tumors that expressed PDPN in mice, and induced PDPN expression in infiltrating host murine cancer associated fibroblasts.

The Oncotarget authors report that human OSCC cells formed tumors that expressed PDPN in mice, and induced PDPN expression in infiltrating host murine cancer associated fibroblasts.

Dr. Gary S. Goldberg from Rowan University said, "Approximately 300,000 new cases of oral cancer are diagnosed each year, causing over 120,000 deaths worldwide".

About 50% of T1 and T2 primary tumors display elevated PDPN expression, and this number increases to about 75% for those at stages T3 and T4. In addition, over 70% of primary OSCC tumors with cervical lymph node metastases express elevated levels of PDPN.

OSCC lethality also correlates with PDPN expression, with undetectable, weak, moderate, and high PDPN expression resulting in 100%, 93%, 70%, and 37% 5-year disease-specific survival rates, respectively.

PDPN promotes OSCC cell motility to drive tumor invasion and metastasis that cause most oral cancer deaths.

Indeed, PDPN expression enhances the motility and invasion of several transformed cell types including mammary carcinoma, glioma, and OSCC.

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

For example, antibodies against PDPN can inhibit the growth and metastasis of tumor cells that express PDPN in mice.

The Goldberg Research Team concluded in their Oncotarget Research Paper that PDPN has emerged as a clear target for oral cancers and precancerous lesions.

They show here that MASL can target PDPN to inhibit OSCC cell growth and motility.

However, targeting of MASL to other sialic acid modified receptors on cancer cells cannot be ruled out.

Interestingly, Maackia amurensis has been used for many centuries as a medicinal plant to treat ailments including cancer.

This work sheds light on potential mechanisms that may be exploited to expand our arsenal of targeted cancer treatments, particularly agents that can be administered orally.

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DOI - https://doi.org/10.18632/oncotarget.3515

Full text - https://www.oncotarget.com/article/3515/text/

Correspondence to - Gary S. Goldberg - gary.goldberg@rowan.edu

Keywords - podoplanin, cancer, cell migration, receptor, lectin

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