This lab primarily focuses its work on studying intercellular communication via cellular extensions called tunneling nanotubes (TnTs, or TNTs, for short). These structures are long, thin, spontaneously forming actin-based cellular extensions that occur in a variety of cell types, including inflammatory cells (e.g. B cells, macrophages), and neurons. More recently, they have been examined in malignant cells. When examined in vitro, TnTs are differentiated from other actin-based structures such as filopodia, invadopodia, and lamellopodia by their characteristic non-adherence to the substratum. Furthermore, once they attach to nearby or distant cells in culture, they form direct connections that serve as conduits for intercellular transport of a variety of cellular cargo and contents, including but not limited to lipophilic vesicles, Golgi vesicles, and even mitochondria. To date, there have been relatively few studies of TnTs in cancer, particularly in primary cancer cells or tumors. Much remains unknown about these structures, including their in vivo relevance.
This team was the first to demonstrate, using confocal microscopy, the presence of nanotubes in intact malignant tumors. To date, these researchers have demonstrated nanotubes in several invasive malignancies such as mesothelioma and lung adenocarcinoma from surgically resected tumors from human patients, and more recently in orthotopic animal models including osteosarcoma. The collaborative team believes that TnTs are an underexplored yet potentially important mode of intercellular communication in cancer and play a heretofore unassessed role in tumor-stromal cross-talk in the complex and heterogeneous tumor microenvironment.