Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Prostate cancer uses Wnt signaling proteins to promote growth of bone tumors

02.09.2005


Prostate cancer is a cruel disease. Left untreated, prostate cancer cells often metastasize, or spread, to bone where they form fracture-prone tumors that are extremely painful.



More than 80 percent of men who die from prostate cancer die with metastatic disease in their bones. But scientists know very little about how migrating prostate cancer cells set up housekeeping in bone tissue and produce the dense bony lesions characteristic of prostate cancer.

Now, new research by scientists at the University of Michigan’s Comprehensive Cancer Center suggests that prostate cancer manipulates an important group of signaling proteins called Wnts (pronounced "wints") to establish itself in bone. By changing the amount and activity of Wnt proteins, prostate cancer cells upset the normal balance between formation and destruction of bony tissue.


"There is strong evidence that Wnt proteins play a central role in regulating normal skeletal development in an embryo," says Christopher L. Hall, Ph.D., a senior research fellow in urology at U-M. "But this is the first time Wnts have been shown to be involved in abnormal bone production in adult animals with prostate cancer."

Hall is first author of a paper to be published in the Sept. 1 issue of Cancer Research, which presents results from U-M studies of Wnt proteins in human prostate cancer cell lines and in laboratory mice injected with prostate cancer cells.

"Normal bone growth and remodeling depends on a controlled balance between production of new bone and resorption of existing bone," says Evan T. Keller, D.V.M., Ph.D., a professor of urology and pathology in the U-M Medical School, who directed the U-M study. "When a tumor forms in bone, it upsets this balance."

Several types of cancer metastasize to bone, according to Keller, but most of them tip the balance toward destruction – producing what scientists call osteolytic lesions, or holes in the bone. Prostate cancer is unique in its ability to trigger increased bone production, which creates what’s called an osteoblastic lesion.

"In metastatic prostate cancer, we think that both processes are going on," Keller says. "Our hypothesis is that prostate cancer cells first induce more bone resorption to help the invading cells become established in bone. But then there’s a switch to increased bone production. Although we don’t know the exact mechanism responsible for the switch, we know that it’s related to the activity of Wnt proteins in prostate cancer cells."

In the first phase of their research, U-M scientists measured the amount of Wnt protein in cells from normal human prostate tissue, localized prostate cancer and metastatic prostate cancer cells. Using the same cell lines, they also looked for the presence of a protein called DKK-1, which is known to inhibit Wnt activity. They discovered that the amounts of Wnt and DKK-1 protein present in human prostate cells varied inversely with the developmental stage of prostate cancer.

"As the cancer progressed, DKK-1 levels went down," Hall says. "Cells with osteoblastic activity had high levels of Wnt activity and low levels of DKK-1, while cells with osteolytic activity showed decreased Wnt activity and high levels of DKK-1."

"Our results suggest that DKK-1 may act like a switch on prostate cancer cell activity," Keller says. "When we altered the cells to increase the amount of active DKK-1, it blocked Wnt’s signal, changing prostate cancer cells from an osteoblastic to a highly osteolytic cell line."

To test their hypothesis, U-M scientists injected human prostate cancer cells into the tibias, or long leg bones, of one group of immune-deficient mice. Twelve weeks later, U-M researchers removed and examined bone tumors from the mice. They found that these mice produced tumors with a dense overgrowth of bone. A second group of mice, injected with prostate cancer cells made to express the Wnt inhibitor, DKK-1, developed highly osteolytic tumor lesions, which destroyed most of the bone.

"This demonstrated that Wnts promote the overproduction of bone by prostate cancer cells," Keller says.

In previous research, the U-M team found that preventing the osteolytic changes associated with bone resorption also prevented prostate cancer from establishing itself in bone. By learning how DKK-1 blocks Wnt’s signal to prostate cancer cells, they hope to learn how to control physical changes in bone that encourage the development of metastatic tumors.

"Our goal is to find ways to manipulate this Wnt pathway to slow the growth of tumors in bone or decrease the tumor-associated pain," Keller says. "We won’t be able to stop the primary tumor from releasing cells, but by preventing early bone resorption, we may be able to prevent metastatic cells from getting a foothold in bone."

In future research, U-M scientists will try to identify which of the nearly 20 known Wnt proteins is involved in bone changes associated with metastatic prostate cancer.

Sally Pobojewski | EurekAlert!
Further information:
http://www.umich.edu

More articles from Life Sciences:

nachricht Decoding the genome's cryptic language
27.02.2017 | University of California - San Diego

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Safe glide at total engine failure with ELA-inside

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

New pop-up strategy inspired by cuts, not folds

27.02.2017 | Materials Sciences

Sandia uses confined nanoparticles to improve hydrogen storage materials performance

27.02.2017 | Interdisciplinary Research

Decoding the genome's cryptic language

27.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>