Guide to Microscopy in Cancer Research

February 04, 2025

Guide to Microscopy in Cancer Research

Research into cancer therapeutics often requires the combination of fluorescence microscopy and innovative functional assays

Cancer is a complex and heterogeneous disease caused by cells deficient in growth regulation. Genetic and epigenetic changes in one or a group of cells disrupt normal function and result in autonomous, uncontrolled cell growth and proliferation.

Imaging has become a key tool in the study of cancer biology. High-resolution imaging is indispensable for the study of genetic and cell signaling changes that underlie cancer, whereas live-cell imaging is crucial for a deeper understanding of function and disease mechanisms. Microscopy techniques are also essential for the study of spatial relationships between different types of tumor cells. They are also important for understanding the role of the immune system in battling cancerous cells. For the latter, researchers rely on multicolor imaging for a faster rate of discovery.

Challenges When Using Imaging To Study Cancer

Optimal temporal and spatial resolution

Research into cancer therapeutics often requires the combination of fluorescence microscopy and innovative functional assays. With optimal temporal and spatial resolution, researchers are able to monitor dynamic events in living cells, such as cell migration and metastasis. These dynamic processes are at the core of cancer development.

Visualizing in real time

Understanding these processes has been challenging due to the difficulty of visualizing tumor cell behavior in real time. Fast imaging over prolonged periods of time tends to come with a sacrifice: either decreased resolution or, more often, harm to your precious specimens. The challenge is finding the imaging technique and system that provides you with the best data with the highest resolution while keeping the cells alive so that you can follow the processes of interest.

Empowering Spatial Biology with Open Multiplexing and Cell DIVE

Spatial biology and multiplexed imaging workflows have become important in immuno-oncology research. Many researchers struggle with study efficiency, even with effective tools and protocols. Here, we…

Multiplexed Cell DIVE imaging to characterize the tumor immune microenvironment in human colon adenocarcinoma (CAC) tissue.

AI-Powered Multiplexed Image Analysis to Explore Colon Adenocarcinoma

In this application note, we demonstrate a spatial biology workflow via an AI-powered multiplexed image analysis-based exploration of the tumor immune microenvironment in colon adenocarcinoma.

Multiplexed Cell DIVE imaging of selected clusters and unique cell populations identified in mucinous cystadenocarcinoma of the ovary.

A Meta-cancer Analysis of the Tumor Spatial Microenvironment

Learn how clustering analysis of Cell DIVE datasets in Aivia can be used to understand tissue-specific and pan-cancer mechanisms of cancer progression

Clustering based analysis reveals various immune cell populations enriched in tumor cells within CT26.WT syngeneic mouse tumor models.

Spatial Architecture of Tumor and Immune Cells in Tumor Tissues

Dig deep into the spatial biology of cancer progression and mouse immune-oncology in this poster, and learn how tumor metabolism can effect immune cell function.

Colon adenocarcinoma and normal colon at the tumor margin. 13 biomarkers shown including Cadherin, CD3, CD4, CD8, CD20, CD31, CD45, Collagen, Caspase 9, BCL2, Beta-Catenin, Vimentin, and Smooth Muscle Actin.

Uncover the Hidden Complexity of Colon Cancer with the Big Data Viewer

Colorectal cancer poses a significant health burden. While surgery is effective initially, some patients develop recurrent secondary disease with poor prognosis, necessitating advanced therapies like…

Multiplexing To Understand Mechanisms of Disease

Multicolor fluorescence microscopy, either confocal or widefield based, is a fundamental tool to understand the spatial context, co-localization, and proximity of multiple biomarkers when studying complex events, such as immunosuppression or angiogenesis. This aim can often be challenging, as there are limits to the number of fluorophores you can successfully distinguish with this “multiplexing” approach.

Fortunately, there are innovative imaging systems and strategies to improve the separation of fluorophores (e.g. FluoSync - a streamlined approach for simultaneous multiplex fluorescent imaging using a single exposure) and increase the number of fluorescent probes to that which is needed in your experiment.

Pancreatic ductal adenocarcinoma tissue section imaged with Cell DIVE.

Finding the Right Tools

Cancer is complex and requires a myriad of methods that include spatiotemporally resolved, live-specimen, and single-cell imaging. More insights into cellular processes concerning cancer will come likely from methods with the highest possible resolution and multiparametric image analysis. Approaches like fluorescence confocal microscopy enable you to study multiple targets within tissues or cellular structures.

Advanced imaging techniques, such as super-resolution or, more recently, lifetime imaging or lightsheet, help you to better understand the molecular interactions and regulatory mechanisms behind tumor initiation, progression, and response to treatment.

Laser microdissection or correlative light and electron microscopy (CLEM) enable the study of spatial receptor arrangements in membranes and genome organization in cell nuclei.

Super-Resolution Microscopy

Super-resolution light microscopy empowers you to study subcellular structures and dynamics with greater detail. While the spatial resolution of confocal image acquisition is doubled with the LIGHTNING technology, when using STED it can deliver insights at the nanoscale. Learn more here about Leica super-resolution methods and how they enable novel discoveries in the fields of virology, immunology, neuroscience, and cancer research.

Fluorescence Microscopy Solutions

Find out how fluorescence microscopes from Leica Microsystems support your research. Fluorescence is one of the most commonly used physical phenomena in biological and analytical microscopy for its high sensitivity and high specificity. Fluorescence is a form of luminescence that through microscopy allows users to determine the distribution of a single molecule species, its amount and its localization inside a cell.

Fluorescence Lifetime Imaging Solutions

Leica Microsystems is at the cutting edge of today’s fluorescence lifetime imaging advances. Our systems make lifetime imaging faster and easier to use than ever before, bringing its advantages to every day confocal imaging experiments.