Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Enzyme eliminated by cancer cells holds promise for cancer treatment

An enzyme that cancer cells eliminate, apparently so they can keep proliferating, may hold clues to more targeted, effective cancer treatment, scientists say.

In a high-stakes tit for tat, protein kinase G enables healthy cells to stay on task to proliferate, differentiate then provide a useful function. Cancer somehow reduces or eliminates PKG and cells get stuck proliferating.

"The bottom line is, in normal tissue, you can see PKG being expressed; but tumors or cell lines that correlate with those tissues don't have nearly as much," says Dr. Darren Browning, cancer researcher at the Medical College of Georgia.

Cell lines used for all types of research appear to support his hypothesis. Many are actually cancer cells because of their proclivity to keep producing; Dr. Browning and others have shown PKG is lost in these cells. "You split them once or twice and they kind of lose their character," he says.

The same appears true for tumors in people, says Dr. Browning, whose lab has found dramatic differences in PKG levels in tumors compared to even nearby, healthy tissue removed in surgery to ensure a cancer-free margin.

The findings made him wonder if the change in PKG level was just an artifact or was critical to cancer survival. "A lot of proteins are lost by cancer cells, so we asked, 'What happens if we put PKG back into the cancer cells?'"

He took metastatic colon cancer cells, created a system for reintroducing PKG, then put the cells into mice without an immune system. He admits he was disappointed that the PKG-enhanced cells grew but became very interested in how they grew.

Cancer cells without PKG created hard, solid tumors that spread. PKG-enhanced cells created a soft, non-invasive tumor that literally fell apart on contact and seemed to grow in little islands. After consultation with pathologists and others, he realized the PKG-enhanced cells were congregating around the few blood vessels. "We know that cancer cells, particularly colon cancer cells, are very aggressive at bringing blood vessels into the tumor," he says. Cells poor at recruiting blood vessels don't grow well, which seems to be the case for PKG-enhanced colon cancer cells.

Now he wants to know how PKG nullifies aggressive metastatic cancer cells. "We think PKG inhibits cancer by getting rid of a cancer-promoting gene called beta-catenin, which slows growth and blocks the tumor's ability to recruit blood vessels that are needed to grow bigger," says Dr. Browning, who recently received a $720,000 American Cancer Society grant to pursue his hypothesis. His proposal was ranked number one by the ACS Cell Structure and Metastasis Study Section.

He's already shown that PKG can reduce vascular endothelial growth factor, or VEGF; anti-VEGF drugs are the focus of numerous anti-cancer trials underway in the country because of VEGF's critical role in development of new blood vessels. "Maybe by activating PKG or increasing PKG expression in tumors, we are going to reduce the amount of VEGF they produce," he says. "We don't know whether PKG has a role in going from normal tissue to the initiation of a tumor, but we think it's important to the tumor both in terms of angiogenesis and blocking metastasis." He points to one of his studies in which colon cancer's spread to the lungs – a common path for metastatic colon cancer – was completely blocked by PKG expression.

A big part of the magic of PKG may be its impact on a gene called beta-catenin, which enables many stem cells, including those in the skin, bone marrow and colon, to proliferate throughout life. Little pits called crypts in the wall of the colon contain Wnt hormone which stimulate nearby stem cells, causing an increase in beta-catenin. The net effect is the colon makes new cells to replace cells lost to the ongoing grind of absorbing water and minerals from food and forming and eliminating waste.

As cells start moving out of the crypt, away from the Wnt hormone, beta-catenin levels go down so cells should stop dividing and start maturing. Essentially all colon cancers have an aberration in this beta-catenin system that prevents normal degradation and allows cell to keep proliferating.

"In the normal cells that line the colon, you don't see very much beta-catenin. We think PKG in these cells keeps it that way to keep the cells from continuing to proliferate and spread," says Dr. Browning, who has already shown that in the test tube at least, adding PKG lowers beta-catenin levels. Interestingly, beta-catenin also is known to regulate VEGF expression in colon cancer.

"In a nutshell, the first and most important genetic lesions leading to colon cancer cause increased beta-catenin levels," says Dr. Browning. "We found PKG can knock down beta-catenin levels by up to 80 percent in some colon cancer cells and we think that is part of the mechanism by which PKG is able to block tumor angiogenesis and metastasis."

He's excited by the implications and is involved in extensive collaborations to understand how PKG regulates beta-catenin and how it might be used in cancer therapies.

Evidence of PKG's effectiveness in fighting colon cancer in humans may already be available. Colon and rectal cancer is the third most common cancer in men and women in the United States but it's rare in developing countries where residents eat less processed food and ingest more bacteria. Some of these bacteria make a protein, STa, which appears to prevent and even kill colon cancer cells. Dr. Browning believes that PKG is responsible for STa's anti-cancer effects.

Toni Baker | EurekAlert!
Further information:

Further reports about: Beta-Catenin Browning PKG PKG-enhanced Vessels colon cancer don'

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

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

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>