Molecular mobility and activity in an intravital imaging setting – implications for cancer progression and targeting

Abstract

Molecular mobility, localisation and spatiotemporal activity are at the core of cell biological processes and deregulation of these dynamic events can underpin disease development and progression. Recent advances in intravital imaging techniques in mice are providing new avenues to study real-time molecular behaviour in intact tissues within a live organism and to gain exciting insights into the intricate regulation of live cell biology at the microscale level. The monitoring of fluorescently labelled proteins and agents can be combined with autofluorescent properties of the microenvironment to provide a comprehensive snapshot of in vivo cell biology. In this Review, we summarise recent intravital microscopy approaches in mice, in processes ranging from normal development and homeostasis to disease progression and treatment in cancer, where we emphasise the utility of intravital imaging to observe dynamic and transient events in vivo. We also highlight the recent integration of advanced subcellular imaging techniques into the intravital imaging pipeline, which can provide in-depth biological information beyond the singlecell level. We conclude with an outlook of ongoing developments in intravital microscopy towards imaging in humans, as well as provide an overview of the challenges the intravital imaging community currently faces and outline potential ways for overcoming these hurdles.

Multidimensional Imaging of Mammary Gland Development: A Window Into Breast Form and Function

“…animals (Pittet and Weissleder, 2011). This powerful approach is increasingly harnessed in experimental and pre-clinical studies in fields spanning developmental biology, immunology, neuroscience, and cancer research (Condeelis and Weissleder, 2010;Nobis et al, 2018). Although currently limited, the utility of high-resolution IVM for clinical use (e.g., in dermatology, laser endomicroscopy) is an active area of research (Coste et al, 2019).…”

Recent advances in understanding the complexities of metastasis

“…Advances in technologies such as intravital imaging have allowed us to uncover mechanisms by which tumour cells manipulate the normal tissues within which they grow in order to facilitate disease progression 59, 118, 119 . Several recent articles have shown the close interplay among CAFs, primary tumour-associated ECM remodelling, and progression of desmoplastic tumours (those surrounded by dense fibrous tissue) such as pancreatic ductal adenocarcinoma 88, 120– 122 and breast cancer 123 .…”

Intravital imaging reveals cell cycle-dependent satellite cell migration during muscle regeneration

“…Intravital imaging by two-photon microscopy is becoming a powerful technique to study the complexity of biological events in living tissues including skeletal muscle (Pittet and Weissleder, 2011); (Nobis et al, 2018). For example, Webster et al developed an intravital imaging technique to observe cells labeled with Pax7-CreERT2 in living mice (Webster et al, 2016).…”