Nonlinear Imaging to Elucidate the Physical and Molecular Mechanisms Regulating Carcinoma Progression

Tuesday, April 30, 2019 - 11:20am - 12:10pm
Lind 305
Paolo Provenzano (University of Minnesota, Twin Cities)
Epithelial cancers, or carcinomas, behave like a complex “organ” and are comprised of multiple cell populations, including primary carcinoma cells, stromal fibroblasts, immune cells, endothelial cells, and structural and signaling components such as the stromal extracellular matrix (ECM). In this complex microenvironment, cells encounter a multitude of coordinated, simultaneously active, stimuli that are biochemical, structural, and mechanical in nature. The presence of these elements is neither random nor uniform across the tumor. Rather, these elements and the dynamic interactions among them evolve coordinately in space and time during tumor progression, conspiring to promote and sustain the carcinoma and contributing to its ability to resist chemical, immune, and radiotherapies. As such, here recent findings elucidating the influence of mechanical and architectural cues in disease progression to metastasis through nonlinear optical imaging with multiphoton excitation and second harmonic generation imaging coupled with quantitative analysis of emission signals will be discussed. Recent findings demonstrating the role of key features of the tumor microenvironments that drive disease progression and play a role in resisting therapeutic intervention through complex stromal dynamics that limit transport of small molecule therapies and anti-tumor immunity will be presented. Further, recent findings highlighting the utility of stroma targeting therapy to alter physical drivers of disease in the stroma and enhance drug delivery and anti-tumor immunity will be presented.