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

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.


'"/>

Source:University of Michigan Health System


Related biology news :

1. First-ever Compounds To Target Only Metastatic Cells Are Highly Effective Against Breast, Prostate, And Colon Cancers
2. Estrogen-like Component of Plastic Stimulates Growth of Certain Prostate Cancer Cells
3. Penn Surgeons Use Completely Robotic Surgery to Successfully Treat Prostate Cancer
4. Viral DNA sequence a possible trigger for breast cancer
5. Enzyme, lost in most mammals, is shown to protect against UV-induced skin cancer
6. Its not all genetic: Common epigenetic problem doubles cancer risk in mice
7. Columbia research lifts major hurdle to gene therapy for cancer
8. Combination therapy boosts effectiveness of telomere-directed cancer cell death
9. Mitochondrial DNA mutations play significant role in prostate cancer
10. New imaging method gives early indication if brain cancer therapy is effective, U-M study shows
11. BRCA1 causes ovarian cancer through indirect, biochemical route
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:1/19/2017)... India , January 19, 2017 According to a ... Opportunities and Forecast, 2014 - 2022," the global biometric sensor market is expected ... 2016 to 2022. In 2015, Asia-Pacific dominated the global ... and private sectors. Continue Reading ... ...
(Date:1/13/2017)... 2017 Sandata Technologies, LLC, a leading ... industry, including Electronic Visit Verification™ (EVV™), announced today ... as Senior Vice President of Product Management. ... homecare experience to Sandata, where he will be ... align Sandata,s suite of solutions with the needs ...
(Date:1/11/2017)... Iowa , Jan. 11, 2017 Intoxalock, ... first with the release of its patent-pending calibration device. ... and reliably perform calibrations, securely upload data logs and ... for the customer. "Fighting drunk driving through ... for the public at large, but also for the ...
Breaking Biology News(10 mins):
(Date:1/24/2017)... (PRWEB) , ... January 24, ... ... the release of Version 5.0 of its award-winning CERF ELN ... a 21CFR11 compliant, collaborative, knowledge asset manager used by laboratories, regulated scientific ...
(Date:1/24/2017)... SANTA CLARA, Calif. , Jan. 24, 2017  Frost & ... chairman of the Fonar Corporation, will receive special recognition at the ... , taking place March 19 to 21, 2017 at the Loews ... To register and download the event agenda for ... www.frost.com/medtech ...
(Date:1/24/2017)... , Jan. 24, 2017   Bracket , a ... announced the addition of Jennifer Peters to ... President and General Manager for the Scientific Services division. ... Bracket,s work in Rater Training, Quality Assurance, and Electronic ... a strong skillset and demonstrated record building technology-based businesses ...
(Date:1/24/2017)... MONTREAL , Jan. 24, 2017 /PRNewswire/ - BioAmber Inc. ... demand, the underwriters have agreed to increase the size of ... stock of the Company, together with warrants to purchase 1,842,106 ... price of US$5.50 per share of common stock (the "Exercise ... share and associated warrant (the "Public Price"). The warrants have ...
Breaking Biology Technology: