The protein podoplanin (PDPN) appears to play a role in promoting tumor progression in malignant pleural mesothelioma (MPM), according to a study in mice, and is likely a good target for treating the disease.
The research, “Podoplanin promotes progression of malignant pleural mesothelioma by regulating motility and focus formation,” was published in the journal Cancer Science.
MPM grows aggressively in the chest or thoracic cavity. Podoplanin (PDPN), a naturally occurring substance that the body produces when MPM is present, has been used to diagnose the disease. Now it appears likely it plays a part in MPM becoming worse.
Researchers discovered that 47 of 52 MPM tumors they examined tested positive for PDPN, along with three of six cell cultures they obtained from MPM tumors. Eliminating PDPN made it harder for the cells to spread in culture.
But increasing PDPN in MPM cells low in PDPN increased motility, or cells’ propensity to spread. PDPN also led to more MPM cell clustering, or focus formation, in laboratory cell cultures.
Researchers confirmed the findings in laboratory mice. Higher PDPN levels in MPM cells impaired the development of a thoracic tumor. In contrast, increasing the levels of the protein in MPM cells that were originally low in PDPN promoted the progression of a thoracic tumor in the mice.
The results showed that PDPN increases cell motility and triggers focus formation in cell cultures. This likely contributed to tumor growth in the chest cavities of mice implanted with MPM tumors that had high levels of PDPN. Together, the results suggest targeting PDNP is a possible strategy for treating MPM.
Looking at the mechanism underlying PDNP tumor-promoting activity, researchers found that MPM tumors with high amounts of PDPN had lower levels of the protein E-cadherin and less activation of the protein YAP-1. E-cadherin prevents tumors from spreading to distant organs, and YAP-1 contributes to cancer. This suggests that PDNP’s role in MPM is related to its regulation of the proteins.
“These findings indicate that PDPN is a diagnostic marker as well as a pathogenetic regulator that promotes MPM progression by increasing cell motility and inducing focus formation. Therefore, PDPN might be a pathogenetic determinant of MPM dissemination and aggressive growth and may thus be an ideal therapeutic target,” the researcher wrote.