I’ve posted a lot of images from papers on human disease models lately, and that’s a good thing. Despite what you may hear from politicians mocking research using fruit flies, worms, or tiny fish, the power of model systems to study a human problem is undeniable to anyone with half a clue. All science on the continuum from basic research all the way to clinical trials is valuable…so thank your favorite scientist today! Today’s image is from a zebrafish paper that identifies a new pathway that may be a good therapy target for muscular dystrophies.
Muscular dystrophies are fairly common diseases that result in the weakening of the protein complexes that connect muscles to their underlying environment, called the extracellular matrix (ECM). The degeneration of muscle-ECM attachment eventually leads to progressive loss of muscle movement and locomotion for the patient. A recent paper identifies a new pathway in muscle-ECM attachment using zebrafish as a model. Goody and colleagues found that biosynthesis of the small molecule NAD+ can reverse muscle degeneration in certain types of dystrophies in zebrafish and even improve swimming. This pathway improves the organization of laminin, an important ECM protein, suggesting the function of an additional laminin receptor complex and pathway from those already studied. Goody and colleagues suggest that this new pathway may serve as a focal point for new muscular dystrophy therapies. In the images above, normal ECM basement membrane tissue adhered normally to both normal muscle cells (blue) and cells with muscle degeneration mutations (red), even after the stress of swimming. This experiment shows the importance of a healthy ECM in restoring function for dystrophic muscles.
Goody, M., Kelly, M., Reynolds, C., Khalil, A., Crawford, B., & Henry, C. (2012). NAD+ Biosynthesis Ameliorates a Zebrafish Model of Muscular Dystrophy PLoS Biology, 10 (10) DOI: 10.1371/journal.pbio.1001409
Understanding how a cell works normally is hard enough for biologists. Understanding how a cancerous cell works is exponentially harder—there are different stages of tumorigenesis and countless different types of cancer and countless different environments within the body. Today’s image is from a study that takes a systematic approach to understanding the interactions between cancerous cells and their environment.
The progression of tumor cells to metastatic cancer cells correlates with poor prognoses for cancer patients. The steps that drive cancer cells to spread (metastasis) are not well understood, but may be effective targets for chemotherapies. For example, tumor cells lose adhesion to their underlying extracellular matrix (ECM) prior to spreading to other regions of the body. Understanding this loss of cell-ECM adhesion may guide the development of new therapies. A recent paper describes the systematic analysis of cell-ECM adhesion in tumor cells by using robotically spotted arrays of 768 paired combinations of ECM molecules. Reticker-Flynn and colleagues monitored the adhesion profiles of lung cancer cell lines at different stages of cancer progression on these arrays of ECM molecules, and found ECM-cell interactions that may be successful therapeutic targets. The images above show an array of spotted ECM protein combinations (visible through immuno- and fluorescent-labeling, top), and examples of cells adhered to the ECM spots (bottom images).
Reticker-Flynn, N., Malta, D., Winslow, M., Lamar, J., Xu, M., Underhill, G., Hynes, R., Jacks, T., & Bhatia, S. (2012). A combinatorial extracellular matrix platform identifies cell-extracellular matrix interactions that correlate with metastasis Nature Communications, 3 DOI: 10.1038/ncomms2128
Adapted by permission from Macmillan Publishers Ltd, copyright ©2012
They invade...they proliferate...they destroy. It sounds like the tagline for a terrible summer blockbuster starring Samuel L. Jackson and an animated sidekick voiced by one of the Kardashians, but it’s the tagline of something far more sinister and real. I’m talking about tumors. Today’s image is from a paper showing how a membrane protein called caveolin-1 can support tumor invasion.
Caveolin-1 is a membrane protein and a major component of caveolae, which are small membrane invaginations that participate in endocytosis. A recent paper finds that caveolin-1 also functions in cell elongation, migration, and invasion by remodeling a cell’s microenvironment (aka “stroma”). Specifically, Goetz and colleagues found that caveolin-1 affects stromal architecture by regulating the activity of Rho GTPase, a signaling protein frequently involved in actin dynamics. This caveolin-1-inspired remodeling of the stroma is significant for tumor biology, too—the stiffness, contractility, and general architecture of a tumor’s stroma can affect its growth, invasion, and metastasis. In the images above, tumor cells (green) were cultured in a 3D-gels with fibroblast cells (red) that expressed caveolin-1 (top row) or did not express caveolin-1(bottom row). When tumor cells were surrounded by caveolin-1-expressing cells, they were able to invade further into the gel.
Goetz, J., Minguet, S., Navarro-Lérida, I., Lazcano, J., Samaniego, R., Calvo, E., Tello, M., Osteso-Ibáñez, T., Pellinen, T., Echarri, A., Cerezo, A., Klein-Szanto, A., Garcia, R., Keely, P., Sánchez-Mateos, P., Cukierman, E., & Del Pozo, M. (2011). Biomechanical Remodeling of the Microenvironment by Stromal Caveolin-1 Favors Tumor Invasion and Metastasis Cell, 146 (1), 148-163 DOI: 10.1016/j.cell.2011.05.040
Copyright ©2011 Elsevier Ltd. All rights reserved.
