Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Stanford scientists identify molecular powerbrokers involved in cancer's spread

You know the guy — he's your Facebook friend. The one who knows everyone. Secure at the center of a dense web of relationships, he suggests causes and reconnects old friends like a skilled matchmaker.

Scientists have known for some time that biological molecules interact with one another in a similarly complex pattern. Now researchers at the Stanford University School of Medicine have determined that hamstringing these molecular powerbrokers is a good way to derail processes such as cancer development.

"It's like social networking," said Paul Khavari, MD, PhD, professor of dermatology at the medical school. "If you take the most highly interconnected person and somehow hinder his access to a computer, the network may fall apart." Although the Stanford researchers were focusing on tumor invasion and metastasis, their expectation is that a similar approach could be used to identify potential targets for many different diseases.

Khavari, who is also a member of Stanford's Cancer Center and Bio-X, is the senior author of the research, which will be published in the June issue of Cancer Cell. He is also the clinical chief of the dermatology service at the Veterans Affairs Palo Alto Health Care System.

Khavari and genetics graduate student Jason Reuter used the concept of biological networks to investigate how cancers progress from a growing lump of unruly cells to an invasive, potentially deadly tumor. They found that inhibiting a molecule called beta-1 integrin blocked the ability of the cells to grow and invade surrounding tissue.

"Ninety percent of all human tumors, including breast, lung, prostate, colon, pancreatic and skin cancers, arise in the epithelial tissue that lines body surfaces," said Khavari. "None of these tumors become highly dangerous to a person unless they invade through the underlying basement membrane and begin to spread to other tissue."

To conduct the research, Khavari and Reuter devised the first-ever three-dimensional model of inducible human tissue tumor development by grafting genetically engineered human skin tissue onto mice with compromised immune systems. They then treated the mice with a compound that activated an introduced cancer-causing gene in the modified human tissue, and monitored gene expression in the tumor and the surrounding tissue as the skin cancer developed and began to invade.

"This approach has been able to recapitulate in real time the progression from normal epithelial tissue to invasive cancer," said Khavari, "and now this model is being used to systematically identify the key genes in this process." He and Reuter identified more than 700 genes whose expression patterns deviated from normal during cancer development. They used an existing database to map the genes into functional networks, which varied as the tumor developed.

"A specific set of genes emerged during early tumor development," said Khavari, "which gave way to others as the tumor began to invade surrounding tissue." During early growth, for example, the researchers identified networks in the cancer cells that were involved in cell division and in the surrounding tissue that were involved in the formation of blood vessels to feed the growing tumor. As the cancer progressed, they saw the emergence of networks involved in cell movement and attachment and in remodeling of the extracellular matrix.

As in the Facebook example, the researches focused on those gene products in the networks that were the most highly connected. Sixteen of the top 25 molecules are found either on the surface or between the tumor cells, indicating that the tumor is actively involved in remodeling its surrounding environment. Beta-1 integrin, a member of a family of proteins involved in mediating attachments between cells, was the third-most well-connected. Khavari and Reuter found that blocking the activity of beta-1, which has been implicated in the growth of several human cancer cell lines, slowed the growth of both established and newly developing tumors in their model and seemed to lead to a more clearly defined border between the tumor cells and the surrounding normal tissue.

"Beta-1 integrin proved important in the co-evolution of the tumor and its supporting framework, the stroma, toward malignancy," said Khavari. He and his lab members plan to continue their analysis of other genes in the network, and to try to optimize their model for other types of cells and cancers. "We are working to build models like this for many other epithelial tissues so we can begin to identify the underlying global mediators of cancer progression."

In addition to Khavari and Reuter, other Stanford researchers involved in the study include postdoctoral scholars Susana Ortiz-Urda, MD, PhD; Anna Pasmooij, PhD; and Markus Kretz, PhD; graduate student John Garcia; research associate Florence Scholl, PhD; and associate professor of dermatology Howard Chang, MD, PhD. The research was funded by the Veterans Affairs Office of Research and Development and by the National Institutes of Health.

The Stanford University School of Medicine consistently ranks among the nation's top 10 medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit The medical school is part of Stanford Medicine, which includes Stanford Hospital & Clinics and Lucile Packard Children's Hospital. For information about all three, please visit

Krista Conger | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht The gene of autumn colours
27.10.2016 | Hokkaido University

nachricht Polymer scaffolds build a better pill to swallow
27.10.2016 | The Agency for Science, Technology and Research (A*STAR)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

The gene of autumn colours

27.10.2016 | Life Sciences

Polymer scaffolds build a better pill to swallow

27.10.2016 | Life Sciences

Greater Range and Longer Lifetime

26.10.2016 | Power and Electrical Engineering

More VideoLinks >>>