Sunday, September 24, 2023
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Researchers who study cancer at the cellular level are offering a peek into their world by sharing images caught under electron microscopes, all collected as part of the National Cancer Institute's Cancer Close Up 2016 project. Examples shown here are both beautifully artistic and scientifically informative.
Image courtesy of National Cancer Institute
Across different cancer types, and even within the same tumor, cancer cells exhibit a wide variety of molecular structures and characteristics. This so-called heterogeneity poses difficult challenges to researchers trying to find better ways of managing the disease. This sample of clinical triple-negative breast cancer is stained for bone morphogenetic protein-11 (red); the Golgi marker GM130 (green); glycosylated proteins (white); and nuclei (blue), illustrating profound molecular heterogeneity. Widefield fluorescence microscopy was used to obtain the image.
Image courtesy of Kevin James, University of Virginia Cancer Center, National Cancer Institute
This image shows a human epithelial cell (DNA in blue) with increased numbers of centrosomes (green) amid a sea of normal cells in interphase. Centrosome amplification can lead to chromosomal instability and an abnormal number of chromosomes. These features are hallmarks of cancer and therefore potential targets for new therapies.
Image courtesy of Ryan A. Denu, University of Wisconsin Carbone Cancer Center, National Cancer Institute
This image shows HeLa cervical cancer cells stained for the cytoskeletal proteins actin (red) and tubulin (green). Cancer cells spread in the body with the help of mutated genes that drive changes in the cells' cytoskeleton—the protein filaments and microtubules that control cell shape and contribute to cell movement. Examining how cancer cells use cytoskeletal proteins to move through the body may lead to targeted therapies that reverse these protein signals. Nuclear DNA appears in blue.
Image courtesy of Scott Wilkinson, Adam Marcus, Winship Cancer Institute at Emory University, National Cancer Institute
Treating cancer in the brain is particularly difficult because most drug molecules are not small enough to penetrate the blood-brain barrier. Researchers wonder whether nanoparticles can serve as a drug-delivery mechanism. This image shows nanoparticles (red) being taken up in the brain of a live rat model with glioblastoma (in green). Nuclear DNA is in blue; tumor-associated macrophages are in white.
Image courtesy of Eric Hoyeon Song, Alice Gaudin, W. Mark Saltzman, Yale Cancer Center, National Cancer Institute
MicroRNAs (miRNAs) are small molecules critical to gene expression. Researchers are creating artificial miRNAs capable of binding to, and silencing, genes associated with cancer. Delivering such miRNAs to their target is another challenge. This image shows self-assembled nanoparticles (in red) carrying miRNAs to an aggressive breast tumor in a mouse model and sticking to the tumor target with the help of an adhesive glue.
Image courtesy of Joao Conde, Nuria Oliva, and Natalie Artzi, Koch Institute for Integrative Cancer Research at MIT, National Cancer Institute
Epifluorescence microscopy of microtentacles forming on the surface of a breast tumor cell in a free-floating microenvironment. Microtentacles may play a role in tumor metastasis by helping cancer cells attach to blood vessel walls in distant parts of the body. New therapies that inhibit microtentacles could help reduce metastasis. Because microtentacles respond rapidly to drug treatments, drugs could be quickly tested for individual patients to improve precision medicine.
Image courtesy of Stuart S. Martin, University of Maryland Greenebaum Cancer Center, National Cancer Institute
When cancer cells metastasize to the bone microenvironment from the primary site, they secrete factors that stimulate osteoclasts both to resorb mineralized bone matrix and release stored growth factors that further enhance the growth of cancer cells. Knowing how cancer cells spread to bone and cause bone destruction is important to finding successful treatment. This image shows a large multinucleated osteoclast (red) resorbing bone matrix (orange) adjacent to cancer cells (blue).
Image courtesy of Khalid Mohammad and Theresa Guise, Indiana University Simon Cancer Center, National Cancer Institute
Shown here is a pseudo-colored scanning electron micrograph of an oral squamous cancer cell (white) being attacked by two cytotoxic T cells (red), part of a natural immune response. Nanomedicine researchers are creating personalized cancer vaccines by loading neoantigens identified from the patient's tumor into nanoparticles. When presented with immune stimulants, this activates the patient's own immune system, leading to expansion of tumor-specific cytotoxic T cells.
Image courtesy of Rita Elena Serda, Duncan Comprehensive Cancer Center at Baylor College of Medicine, National Cancer Institute
This image of a breast cancer tumor and its microenvironment was obtained from a live mouse model using multiphoton microscopy and endogenous fluorescence. That is, the image was obtained without any fluorophores, stains, or dyes, using only the metabolic co-factors of NADH and FAD, which are already inside of cells, along with second harmonic generation to see collagen. This technique has important clinical potential for patients who require label-free imaging, and may lead to more effective diagnoses and treatments. Tumor cells display in cyan, macrophages in red, collagen fibers in green.
Image courtesy of Joseph Szulczewski, David Inman, Kevin Eliceiri, and Patricia Keely, Carbone Cancer Center at the University of Wisconsin, National Cancer Institute
Infection with certain types of human papillomavirus (HPV) is associated with various cancers. Researchers are working to understand the processes by which HPV can transform a healthy cell into a cancerous one. This image shows actin (stained in green), a protein involved in cell motion, in HPV-16 E6- and E7-expressing human foreskin keratinocytes.
Image courtesy of Ewa Krawczyk, Georgetown Lombardi Comprehensive Cancer Center, National Cancer Institute
A high level of the critical gene Sox10 is tied to aggressive breast cancer. In parts of the adult mammary gland, Sox10 is expressed in cells with higher levels of stem cell activity and not in mature cells that lack detectable stem cell activity. Progesterone receptor (red) indicates non-stem-like mammary cells, which show an inverse correlation with cells expressing Sox10 (blue). A protein called cytokeratin-8 (green) shows the development of the gland.
Image courtesy of Geoffrey Wahl, Christopher Dravis, Salk Institute, National Cancer Institute
In this image from a genetically engineered mouse model, lung cancer driven by the KRAS oncogene shows up in purple. As a key driver in many types of cancer, the KRAS gene makes a promising target for new cancer therapies.
Image courtesy of Eric Snyder, Huntsman Cancer Institute at the University of Utah, National Cancer Institute
As shown here, lung cancer is associated with a vast stromal desmoplastic reaction (the "neighborhood") in which the connective tissue, associated with the tumor, thickens similarly to scars. Cancer is in red; cell nuclei in cyan; stroma/desmoplasia in green; and an active stroma-specific marker in purple.
Image courtesy of Neelima Shah, Edna Cukierman, Fox Chase Cancer Center, National Cancer Institute
Organoids are miniature versions of organs grown in the lab. Organoid culture systems offer a powerful platform for the development of targeted therapies and precision medicine by letting scientists easily create genetic or environmental changes (difficult or impossible in animal models or human patients) to identify networks of genes that control cellular behaviors that give way to tumors. This image shows an organoid that was grown from a single mammary stem cell. Researchers used this system to demonstrate how a single critical gene, called Sox10 (in blue), controls whether cells turn into dangerous mini "factories," rapidly churning out more copies and variants of themselves. The Sox10 gene allows cells to migrate and to take on characteristics of other cells (plasticity). In cancer cells, these features lead to metastasis and drug resistance. Inner keratin-8+ luminal cells (in green) are surrounded by peripheral keratin-14+ basal cells (in red).
Image courtesy of Geoffrey Wahl, Christopher Dravis, Salk Institute, National Cancer Institute
Human tumors often include slowly proliferating cancer cells that resist treatment. This image shows a cluster of slow-cycling (AKT-low/Hes1-high) breast cancer cells (red) within a human ER+ primary breast tumor (cell nuclei in blue; rapidly cycling, AKT-high, cancer cells in green). Cancer cells enter an AKT-low state in response to decreased interaction of cell surface beta-1 integrin with the extracellular matrix. AKT-low cancer cells within invasive breast cancer tumors persist after combination chemotherapy and contribute to tumor progression.
Image courtesy of Sheheryar Kabraji, Sridhar Ramaswamy, Dana-Farber Harvard Cancer Center at Massachusetts General Hospital, National Cancer Institute
This image shows pancreatic cancer cells (nuclei in blue) growing as a sphere encased in membranes (red). By growing cancer cells in the lab, researchers can study factors that promote and prevent the formation of deadly tumors.
Image courtesy of Min Yu (Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC), USC Norris Comprehensive Cancer Center, National Cancer Institute
This image shows a triple-negative breast cancer cell undergoing retraction and apoptosis (cell death) after treatment with a combination of the chemotherapy drug cisplatin and a mitochondrial division inhibitor drug called mdivi-1. Actin in red; mitochondria in green; nuclei in blue. Understanding how drugs work at the molecular level contributes to better cancer treatments.
Image courtesy of Wei Qian, University of Pittsburgh Cancer Institute, National Cancer Institute
Vista is a molecule that regulates T lymphocytes and plays an important role in immunity. Understanding more about Vista's functional role could help researchers develop immunotherapy approaches to the management of human cancer. This image shows a section of placenta tissue, specifically the cells that line villi of placenta. The yellow color represents the presence of Vista protein; red represents the presence of CD8 protein; blue represents the cell nucleus. This assay shows that the Vista molecule is positively present in cells of the placenta, indicating that placenta can be used as control tissue for immunofluorescent staining assay of Vista in cancer research studies.
Image courtesy of Tin Htwe Thin, Tisch Cancer Institute at the Mount Sinai School of Medicine, National Cancer Institute
In this image from a mouse model of ovarian cancer, optically cleared tumor excised from a murine SKOV tumor seeded with CD63+ cells reveals a high-resolution landscape of the three-dimensional tumor-stromal interfaces that comprise the tumor microenvironment (TME). Second harmonic signal (blue) and autofluorescent/GFP signals (green) demonstrates the interplay of collagen II fibrils and vessels generated from angiogenesis. The use of optical tissue clearing has the potential to greatly improve researchers' ability to assess the anatomic, structural, and cellular constituents that govern metastatic colonization in the TME at a single-cell resolution.
Image courtesy of Chris Booth, Kyle Cowdrick, Frank C. Marini, Comprehensive Cancer Center of Wake Forest University, National Cancer Institute
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