CD142 Identifies Neoplastic Desmoid Tumor Cells, Uncovering Interactions Between Neoplastic and Stromal Cells That...

Area of Science:

• Cancer Biology
• Tumor Microenvironment
• Mesenchymal Tumors

Background:

• Distinguishing neoplastic (tumor) from stromal (non-tumor) cells in mesenchymal tumors is difficult due to a lack of specific markers.
• Understanding tumor-stroma interactions is crucial for cancer progression and treatment.
• Desmoid tumors are mesenchymal neoplasms characterized by beta-catenin stabilizing mutations.

Purpose of the Study:

• To identify surface markers that can differentiate between mutant neoplastic cells and stromal cells in desmoid tumors.
• To develop a method for quantifying and isolating these distinct cell subpopulations.
• To investigate the role of soluble factors in tumor-stroma interactions.

Main Methods:

• High-throughput surface antigen screening of single-cell-derived colonies from human desmoid tumors.
• Utilizing CD142 as a marker for mutant cell identification and isolation via cell sorting.
• Analysis of the secretome of mutant and nonmutant fibroblastic cells.

Main Results:

• CD142 was identified as a highly expressed marker on mutant desmoid tumor cells, correlating with beta-catenin activity.
• CD142-based cell sorting successfully isolated mutant populations, even from samples where mutations were not previously detected.
• PTX3, a stroma-derived factor, was found to enhance mutant cell proliferation through STAT6 activation.

Conclusions:

• A sensitive method using CD142 has been established to quantify and distinguish neoplastic from stromal cells in mesenchymal tumors.
• This approach facilitates the study of tumor-stroma interactions and the identification of regulatory soluble factors.
• Stromal-derived factors like PTX3 represent potential therapeutic targets for modulating mutant cell proliferation.