Featured Research

from universities, journals, and other organizations

3-D Model Reveals Secrets Of Metastasis

Date:
July 12, 2006
Source:
Whitehead Institute for Biomedical Research
Summary:
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.

Researchers tracked the movement of human prostate tumor cells, such as those below, in a 3D matrix. The right column shows software (Imaris) rendering of the cells, which changed shape as scientists altered their environment and increased the concentration of the anti β1 mAB 4B4 surface protein.
Credit: Image s by Muhammad Zaman

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.

“Our findings help explain why two-dimensional assays for metastasis-inhibiting drugs do not effectively predict their effects in tissue,” says Douglas Lauffenburger, who is director of MIT’s Biological Engineering Division.

“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’, 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 MIT’s 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 wasn’t 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.”

The research was funded by the National Institutes of Health, the National Science Foundation and the Sokol Foundation for Cancer Research.


Story Source:

The above story is based on materials provided by Whitehead Institute for Biomedical Research. Note: Materials may be edited for content and length.


Cite This Page:

Whitehead Institute for Biomedical Research. "3-D Model Reveals Secrets Of Metastasis." ScienceDaily. ScienceDaily, 12 July 2006. <www.sciencedaily.com/releases/2006/07/060712073926.htm>.
Whitehead Institute for Biomedical Research. (2006, July 12). 3-D Model Reveals Secrets Of Metastasis. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/2006/07/060712073926.htm
Whitehead Institute for Biomedical Research. "3-D Model Reveals Secrets Of Metastasis." ScienceDaily. www.sciencedaily.com/releases/2006/07/060712073926.htm (accessed July 30, 2014).

Share This




More Health & Medicine News

Wednesday, July 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Xtreme Eating: Your Daily Caloric Intake All On One Plate

Xtreme Eating: Your Daily Caloric Intake All On One Plate

Newsy (July 30, 2014) The Center for Science in the Public Interest released its 2014 list of single meals with whopping calorie counts. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



      Save/Print:
      Share:

      Free Subscriptions


      Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

      Get Social & Mobile


      Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

      Have Feedback?


      Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
      Mobile: iPhone Android Web
      Follow: Facebook Twitter Google+
      Subscribe: RSS Feeds Email Newsletters
      Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins