Navigation Links
3-D model reveals secrets of metastasis

A cancer cell breaks away from a primary tumor and settles in a new location, where it once again divides. Pharmaceutical companies typically use simplistic two-dimensional assays for this process, which is known as metastasis, to evaluate anti-cancer therapeutics. In these assays, cells crawl across the surface of a matrix, traveling in a single plane. But a new study indicates that this approach misses some crucial phenomena.

Working in the labs of Whitehead Member Paul Matsudaira and MIT professor Douglas Lauffenburger, postdoctoral researcher Muhammad Zaman discovered that cells move quite differently in three dimensions. His study, which focused on human prostate tumor cells, appeared this week in the online early edition of Proceedings of the National Academy of Sciences.

"Two-dimensional assays ignore the obstacles that cells face in their natural contexts," explains Zaman, who recently became an assistant professor at the University of Texas at Austin. "In 3D, cells move through a thick jungle of fibers, or "vines"TM, that hinder forward progress."

Cells must either squeeze through or chop up these putative vines to get anywhere. As a result, they move slower in three dimensions.

In an interesting twist, all cells need at least some vines to move, as they latch onto the "branches" with claw-like proteins called integrins and pull themselves forward. When Zaman disabled some of these claws, in a manner analogous to certain anti-cancer drugs, the cells moving across the top of the jungle canopy (in two dimensions) needed a greater number of vines to keep up their pace, while cells plowing through the jungle instead needed vines chopped to maintain the same speed. The complexity of this situation is further increased in that the cells become dramatically sensitive to the stiffness of the vines when the integrins are disabled and consequently tend to squeeze through the vines rather than pushing them aside.

"Our findings help explain why two-dimensional assays for metastasis-inhibiting drugs do not effectively predict their effects in tissue," says Lauffenburger, who is director of MITâ?super>TMs Biological Engineering Division. He believes pharmaceutical companies will eventually use three-dimensional assays, accompanied by appropriate computational models such as that also recently published by Zaman (in Biophysical Journal in 2005), to determine how drugs affect metastasis.

But technology must improve before more complicated 3D studies are attempted. For his 3D work Zaman worked with one sample at a time, using a special confocal microscope at the Whitehead-MIT BioImaging Center. The microscope divided each specimen into virtual slices, generating a new stack of images every 15 minutes.

"It took me about a year to get enough data because the microscope wasnâ?super>TMt designed for high-throughput experiments," he says. Fortunately, the BioImaging Center has one of the most powerful sets of computers at MIT and the imaging processing and analysis went quite quickly.

"Muhammad was successful for two reasons," says Matsudaira. "His computational model predicted what would happen in virtual experiments and then he was able to go straight to test the predictions with these complicated 3D experiments. As a result, the sophisticated models of cell movement enhance our understanding of key biological processes, including metastasis."
'"/>

Source:Whitehead Institute for Biomedical Research


Related biology news :

1. Scientists identify new model Of NK cell development
2. Genrate: a generative model that finds and scores new genes and exons in genomic microarray data
3. Molecular models advance the fight against malaria
4. NYU and MSKCC research provides model for understanding chemically induced cancer initiation
5. Genetic therapy reverses nervous system damage in animal model of inherited human disease
6. Disease progression model of pancreatic cancer developed by Penn researchers
7. A new way to share models of biological systems
8. Understanding biases in epidemic models important when making public health predictions
9. Climate model links higher temperatures to prehistoric extinction
10. Gene therapy advance treats hemophilia in mouse models
11. Targeting a key enzyme with gene therapy reversed course of Alzheimers disease in mouse models

Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/30/2017)... 30, 2017  On April 6-7, 2017, Sequencing.com will ... hackathon at Microsoft,s headquarters in ... focus on developing health and wellness apps that provide ... the Genome is the first hackathon for personal ... largest companies in the genomics, tech and health industries ...
(Date:3/27/2017)... N.Y. , March 27, 2017  Catholic ... Information and Management Systems Society (HIMSS) Analytics for ... EMR Adoption Model sm . In addition, CHS ... of U.S. hospitals using an electronic medical record ... for its high level of EMR usage in ...
(Date:3/22/2017)... 2017   Neurotechnology , a provider of ... announced the release of the SentiVeillance 6.0 ... facial recognition using up to 10 surveillance, security ... The new version uses deep neural-network-based facial detection ... utilizes a Graphing Processing Unit (GPU) for enhanced ...
Breaking Biology News(10 mins):
(Date:5/23/2017)... (PRWEB) , ... May 23, ... ... offer an unlimited source of human cardiovascular cells for research and the ... methods makes it possible to generate large numbers of cardiomyocytes (hPSC-CMs). Due ...
(Date:5/23/2017)... ... 2017 , ... Energetiq Technology, a world leader in high ... accommodate its rapid growth. , The renovations at the company’s headquarters in Woburn, ... areas. The expansion includes, a state-of-the-art engineering facility, and a second clean manufacturing ...
(Date:5/22/2017)... ... ... Stratevi, a boutique firm that partners with healthcare companies to creatively develop and ... downtown Boston at 745 Atlantic Ave. , “We are seeing that even the ... value they provide, not just to patients, but also payers. Having a presence in ...
(Date:5/19/2017)... ... , ... In response to the strong base of evidence supporting the use ... release of their Gait Trainer 3 with an Integrated Music Therapy option. This is ... in rehabilitating individuals with cerebral palsy, traumatic brain injury, stroke and Parkinson’s disease. ...
Breaking Biology Technology: