PAEP functions as an immune modulator to regulate tumor metastasis

Authors

• RGM Buenaventura
• W Chen
• G Merlino
• Y Yu

Abstract

Most cancer-related deaths are associated with the complex phenotypic behavior of metastasis. While it has been established that the tumor microenvironment can affect how cancer grows and spreads, the molecular mechanism by which the metastatic tumors survive and escape from immune attack in the tumor microenvironment remains unclear. To study the molecular mechanism of interaction between metastatic tumors and the immune system in metastasis, we established immune-resistant metastatic models. We identified that PAEP, a progestogen-associated endometrial protein, is significantly upregulated in immune-resistant metastatic tumors compared with non-immune-resistant tumors. PAEP is a glycoprotein that inhibits cell immune function and plays an essential role in the pregnancy process. To examine the function of PAEP in tumor metastasis, we first introduced PAEP into non-immune resistant and poorly metastatic melanoma and rhabdomyosarcoma (RMS) cells. We found that overexpression of PAEP significantly promotes tumor metastatic potential of both melanoma and RMS cells in immunocompetent mice. Interestingly, there was no difference in metastasis between the control and overexpression groups in immunodeficient mice. These data suggest that PAEP may mediate tumor metastasis relating to host immunity. To further confirm the function of PAEP in tumor metastasis, we used CRISPR/Cas9 technology to knockout endogenous PAEP and will test the metastatic potential in different hosts. We will also investigate the molecular mechanisms using RNA sequencing and Digital Spatial Profiling to analyze the metastatic samples. Our study will uncover a new mechanism for how tumors survive in the microenvironment and identify a novel target for the treatment of metastatic diseases.

Scientific Focus Area: Cancer Biology

This page was last updated on Monday, September 25, 2023