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Posts Tagged ‘3D extracellular matrix’


3D Imaging of Cancer Cells

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

3D Imaging of Cancer Cells Could Lead to Improved Ability of Pathologists and Radiologists to Plan Cancer Treatments and Monitor Cell Interactions

Dark Daily Apr 8th 2016        Jon Stone

https://www.linkedin.com/pulse/3d-imaging-cancer-cells-could-lead-improved-ability-plan-joseph-colao

 

3D Imaging of Cancer Cells Could Lead to Improved Ability of Pathologists and Radiologists to Plan Cancer Treatments and Monitor Cell Interactions.

New technology from researchers at the University of Texas Southwestern Medical Center enables the ability to study cancer cells in their native microenvironments.

Imaging research is one step closer to giving clinicians a way to do high-resolution scans of malignant cells in order to diagnose cancer and help identify useful therapies. If this technology were to prove successful in clinical studies, it might change how anatomic pathologists and radiologists diagnose and treat cancer.

Researchers at the University of Texas Southwestern Medical Center developed a way to create near-isotropic, high-resolution scans of cells within their microenvironments. The process involves utilizing a combination of two-photonBessel beams and specialized filtering.

New Imaging Approach Could be Useful to Both Pathologists and Radiologists

In a recent press release, senior author Reto Fiolka, PhD, said “there is clear evidence that the environment strongly affects cellular behavior—thus, the value of cell culture experiments on glass must at least be questioned. Our microscope is one tool that may bring us a deeper understanding of the molecular mechanisms that drive cancer cell behavior, since it enables high-resolution imaging in more realistic tumor.”

In a study in Developmental Cell, Erik S. Welf, PhD, et al, described the new microenvironmental selective plane illumination microscopy (meSPIM). When developing the technology, the team outlined three goals:

1. The microscope design must not prohibitively constrain microenvironmental properties.

2. Spatial and temporal resolution must match the cellular features of interest.

3. Spatial resolution must be isotropic to avoid spatial bias in quantitative measurements.

This new technology offers pathologists and medical laboratory scientists a new look at cancer cells and other diseases. The study notes that meSPIM eliminates the influence of stiff barriers, such as glass slide covers, while also allowing a level of control over both mechanical and chemical influences that was previously impossible.

Early meSPIM Research Reveals New Cell Behaviors

Early use of meSPIM in observing melanoma cells is already offering new insights into the relationship between the cell behavior of cellular- and subcellular-scale mechanisms and the microenvironment in which these cells exist. The study notes, “The ability to image fine cellular details in controllable microenvironments revealed morphodynamic features not commonly observed in the narrow range of mechanical environments usually studied in vitro.”

One such difference is the appearance of blebbing. Created by melanoma cells and lines, these small protrusions are thought to aid in cell mobility and survival. Using meSPIM, observers could follow the blebbing process in real-time. Formation of blebs on slides and within an extracellular matrix (ECM) showed significant differences in both formation and manipulation of the surrounding microenvironment.

The team is also using meSPIM to take a look at membrane-associated biosensor and cytosolic biosensor signals in 3D. They hope that investigation of proteins such as phosphatidylinositol 3-kinase (PI3K) and protein kinase C will help to further clarify the roles these signals play in reorientation of fibroblasts.

meSPIM combined with computer vision enables imaging, visualization, and quantification of how cells alter collagen fibers over large distances within an image volume measuring 100 mm on each side. (Photo Copyright: Welf and Driscoll et al.)

The research team believes this opens new possibilities for studying diseases at a subcellular level, saying, “Cell biology is necessarily restricted to studying what we can measure. Accordingly, while the last hundred years have yielded incredible insight into cellular processes, unfortunately most of these studies have involved cells plated onto flat, stiff surfaces that are drastically different from the in vivo microenvironment …

“Here, we introduce an imaging platform that enables detailed subcellular observations without compromising microenvironmental control and thus should open a window for addressing these fundamental questions of cell biology.”

Limitations of meSPIM

One significant issue associated with the use of meSPIM is the need to process the large quantity of data into useful information. Algorithms currently allow for automatic bleb detection. However, manual marking, while time consuming, still provides increased accuracy. Researchers believe the next step in improving the quality of meSPIM scans lie in computer platforms designed to extract and process the scan data.

Until this process is automated, user bias, sample mounting, and data handling will remain risks for introducing errors into the collected data. Yet, even in its early stages, meSPIM offers new options for assessing the state of cancer cells and may eventually provide pathologists and radiologists with additional information when creating treatment plans or assessments.

 

Seeing cancer cells in 3-D (w/ Video)

http://phys.org/news/2016-02-cancer-cells-d-video.html

 

Cancer in 3-D

http://cdn.phys.org/newman/csz/news/800/2016/cancerin3d.png

Extracted surfaces of two cancer cells. (Left) A lung cancer cell colored by actin intensity near the cell surface. Actin is a structural molecule that is integral to cell movement. (Right) A melanoma cell colored by PI3-kinase activity near the cell surface. PI3K is a signaling molecule that is key to many cell processes. Credit: Welf and Driscoll et al.

Cancer cells don’t live on glass slides, yet the vast majority of images related to cancer biology come from the cells being photographed on flat, two-dimensional surfaces—images that are sometimes used to make conclusions about the behaviour of cells that normally reside in a more complex environment. But a new high-resolution microscope, presented February 22 in Developmental Cell, now makes it possible to visualize cancer cells in 3D and record how they are signaling to other parts of their environment, revealing previously unappreciated biology of how cancer cells survive and disperse within living things.

“There is clear evidence that the environment strongly affects cellular behavior—thus, the value of cell culture experiments on glass must at least be questioned,” says senior author Reto Fiolka, an optical scientist at the University of Texas Southwestern Medical Center. “Our is one tool that may bring us a deeper understanding of the molecular mechanisms that drive cancer cell behavior, since it enables high-resolution imaging in more realistic tumor environments.”

Read more at: http://phys.org/news/2016-02-cancer-cells-d-video.html#jCp

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How Cancer Cells “Grab” Neighbors and “Reel them in”

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

How cancer cells form tumors by reaching out with ‘cables’ and grabbing cells

A cancer riddle solved; counters “cancer stem cell” explanation
January 27, 2016  http://www.kurzweilai.net/how-cancer-cells-form-tumors-by-reaching-out-with-cables-and-grabbing-cells

https://youtu.be/5JToZT_xSyo

University of Iowa | Cancer cells’ motion and accretion into tumors

Two University of Iowa studies have recorded the movements of cancerous human breast tissue cells in real time and in 3D — the first time cancer cells’ motion and accretion into tumors has been continuously tracked, the researchers believe.

The team discovered that cancerous cells, moving at move at 92 micrometers per hour (about twice the speed of healthy cells), actively recruit healthy cells into tumors by extending a kind of cable to grab their neighbors — both cancerous and healthy — and reel them in. Surprisingly, as little as five percent of cancerous cells are needed to form the tumors, a ratio previously unknown.

“It’s not like things sticking to each other,” said David Soll, biology professor at the UI and corresponding author on the open-access paper, published in the American Journal of Cancer Research. “It’s that these cells go out and actively recruit. It’s complicated stuff, and it’s not passive. No one had a clue that there were specialized cells in this process, and that it’s a small number that pulls all the rest in.”

The findings could lead to a more precise identification of tumorigenic cells (those that form tumors) and to testing which antibodies would be best equipped to eliminate them.*

How cancer cells “know” what to do

The question is: how do these cells know what to do. Soll hypothesizes they’re reaching back to a primitive past, when these cells were programmed to form embryos. If true, perhaps the cancerous cells — masquerading as embryo-forming cells — recruit other cells to make tissue that then forms the layered, self-sustaining architecture needed for a tumor to form and thrive. “It’s as if it’s building its own defenses against the body’s efforts to defeat them.”

http://www.kurzweilai.net/images/Cancer-Cells-50-105-hours-stacked.png

University of Iowa researchers have documented how cancerous tumors form by tracking in real time the movement of individual cells in 3-D. They report that just 5 percent of cancer cells are needed to form tumors, a ratio that heretofore had been unknown. (credit: Soll Laboratory)

In the AJCR paper, the researchers found support for their previous observation that tumorigenic cell lines and fresh tumor cells possess the unique capacity to form tumors by the active formation of cellular cables.

The finding lends more weight to the idea that tumors are created concurrently, in multiple locations, by individual clusters of cells that employ the cancer-cell cables to draw in more cells and enlarge themselves. Some have argued that tumors come about more by cellular changes within the masses, known as the “cancer stem cell theory.”

The Developmental Studies Hybridoma Bank funded the study.

* Soll’s Monoclonal Antibody Research Institute and the Developmental Studies Hybridoma Bank, created by the National Institutes of Health as a national resource, directed by Soll and housed at the UI, together contain one of the world’s largest collections of antibodies that could be used for the anti-cancer testing, based on the new findings.


Abstract of Mediated coalescence: a possible mechanism for tumor cellular heterogeneity

Recently, we demonstrated that tumorigenic cell lines and fresh tumor cells seeded in a 3D Matrigel model, first grow as clonal islands (primary aggregates), then coalesce through the formation and contraction of cellular cables. Non-tumorigenic cell lines and cells from normal tissue form clonal islands, but do not form cables or coalesce. Here we show that as little as 5% tumorigenic cells will actively mediate coalescence between primary aggregates of majority non-tumorigenic or non-cancerous cells, by forming cellular cables between them. We suggest that this newly discovered, specialized characteristic of tumorigenic cells may explain, at least in part, why tumors contain primarily non-tumorigenic cells.

 

 

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3D “Squeeze” Helps Adult Cells Become Stem Cells

Reported by: Irina Robu, PhD

Scientists based at Ecole Polytechnique Fédérale de Lausanne led by Matthias Lutolf have been engineering 3D extracellular matrices—gels. These scientists report that they have developed a gel that boosts the ability of normal cells to revert into stem cells by simply “squeezing” them.

The detail of the scientists’ work appeared in Nature Materials, January 11, 2015 in an article entitled, “Defined three-dimensional microenvironments boost induction of pluripotency.” According to the authors they find that the physical cell confinement imposed by the 3D microenvironment boosts reprogramming through an accelerated mesenchymal-to-epithelial transition and increased epigenetic remodeling. They concluded that 3D microenvironmental signals act synergistically with reprogramming transcription factors to increase somatic plasticity.

The researchers discovered that they could reprogram the cells faster and more efficiently  by simply adjusting the composition, hence the stiffness and density of the surrounding gel. As a result, the gel exerts different forces on the cells, “squeezing” them.

The scientists propose that the 3D environment is key to this process, generating mechanical signals that work together with genetic factors to make the cell easier to transform into a stem cell. The technique can be applied to a large number of cells to produce stem cells on an industrial scale.

Source

http://www.genengnews.com/gen-news-highlights/3d-squeeze-helps-adult-cells-become-stem-cells/81252223/

 

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