Oncologists have long puzzled over the fact that after cancer treatment, disseminated tumor cells are quick to grow and form secondary tumors in certain organs, while in other organs they metastasize more slowly. Such is the case with head and neck squamous cell carcinoma (HNSCC) cells, which remain dormant when lodged in bone marrow but rapidly form tumors when they make their way into the lungs.
A study published by Nature Cell Biology, TGF beta 2 dictates disseminated tumour cell fate in target organs through TGF-beta-RIII and p38 alpha/beta signalling by Paloma Bragado, Yeriel Estrada, Falguni Parikh, Sarah Krause, Carla Capobianco, Hernan G. Farina, Denis M. Schewe, and Julio Aguirre-Ghiso, reveals that bone marrow contains high levels of TGF beta 2, which activates the tumor suppressor gene p38 in tumor cells and triggers a cascade of events that renders tumor cells dormant and keeps HNSCC growth in check. In the lungs, where TGF beta 2 is in short supply, these cells rapidly form tumors.
The research team, led by Julio A. Aguirre-Ghiso, PhD, is the first to identify the role of TGF beta 2 in determining whether HNSCC cells will remain harmlessly dormant or behave aggressively in a given location. These findings may have implications for estrogen-positive breast tumor cells, which have a similar genetic signature to that of dormant HNSCC cells. The study provides a clear molecular mechanism and confirms a century-old theory called the “seed and soil” theory of metastasis, which suggests that a tumor cell – the seed – either sleeps or thrives within the unique environment of each organ – the soil.