Tumors are highly heterogeneous entities composed of malignant and stromal cells functioning together as an invasive unit. Effective and efficient intercellular crosstalk in the three-dimensional complex tumor microenvironment is essential for cancer progression. A relatively new mechanism of intercellular communication has been identified in the form of a unique cellular protrusion called tunneling nanotubes (TNTs). TNTs are ultrafine (50-800 nm in diameter), long, non-adherent filamentous actin-based protrusions of the plasma membrane that can serve as intercellular bridges. They can aid in the sharing of proteins, genes, and other cargo between cells. In cancer, TNTs are particularly prevalent and have been shown to facilitate cargo transfer in tumors in vitro and in vivo, but their ultimate role in cancer progression remains unclear. The overall goal of this doctoral thesis work was to investigate the role of TNTs in the context of tumor heterogeneity, tumor metastasis, resistance to chemotherapeutic drugs, and the ability of TNT-mediated communication in conditions such as hypoxia that are typical of the tumor microenvironment. If intercellular communication via TNTs proves to be critical to tumor invasion and the development of treatment-resistance, then preventing or disrupting this communication mechanism represents a potential novel therapeutic strategy for treating cancers.
University of Minnesota Ph.D. dissertation. February 2018. Major: Integrative Biology and Physiology. Advisor: Emil Lou. 1 computer file (PDF); vii, 148 pages.
The role of tunneling nanotubes in mediating intercellular communication in cancer.
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