Debolina Ganguly, Marcel O Schmidt, Morgan Coleman, Tuong-Vi Cindy Ngo, Noah Sorrelle, Adrian T A Dominguez, Gilbert Z Murimwa, Jason E Toombs, Cheryl Lewis, Yisheng V Fang, Fatima Valdes-Mora, David Gallego-Ortega, Anton Wellstein, Rolf A Brekken
Metastatic cancer cells adapt to thrive in secondary organs. To investigate metastatic adaptation, we performed transcriptomic analysis of metastatic and non-metastatic murine breast cancer cells. We found that pleiotrophin (PTN), a neurotrophic cytokine, is a metastasis-associated factor that is expressed highly by aggressive breast cancers. Moreover, elevated PTN in plasma correlated significantly with metastasis and reduced survival of breast cancer patients. Mechanistically, we find that PTN activates NF-κB in cancer cells leading to altered cytokine production, subsequent neutrophil recruitment, and an immune suppressive microenvironment...
May 1, 2023: Journal of Experimental Medicine