Navigation Links
Inflammation Promotes Metastasis of Prostate Cancer

A new research strongly suggests that inflammation associated with the progression of tumors actually plays a key role in the metastasis of prostate cancer.//

According to this research conducted at the University of California, San Diego (UCSD) School of Medicine "mounting an immune response" or "having your body fight the cancer" may not be a good thing.

The research, appearing online March 19 in advance of publication in the journal Nature, was conducted by Michael Karin, Ph.D., and colleagues, identifies a mechanism which triggers metastasis, which is the spread of cancer in late stages of prostate cancer development.

Furthermore, this new work may lead to development of anti-metastatic therapies.

A major hypothesis in cancer research has been that whether the cancer metastisizes or not is determined by genetic changes within the cancer cell itself. But this hypothesis didn't explain why metastases appear many years after the initial tumor.

"Our findings suggest that promoting inflammation of the cancerous tissue, for instance, by performing prostate biopsies, may, ironically, hasten progression of metastasis," said Karin. "We have shown that proteins produced by inflammatory cells are the 'smoking gun' behind prostate cancer metastasis. The next step is to completely indict one of them."

One in six men will be diagnosed with prostate cancer, and one in 33 will die of metastatic disease. Early tumors confined to the prostate can be treated, but no effective treatments are available for metastatic disease, according to Steven L. Gonias, M.D., Ph.D., professor and chair of the UCSD Department of Pathology, a study investigator.

"This study helps explain the paradox that, in certain types of malignancy, inflammation within a cancer may be counterproductive," said Gonias.

In research using mouse models and confirmed in human tissue, the scientists observed that a protein kinase cal led IkB kinasea (IKKa) turns down the expression of a single gene called Maspin, which has well-established anti-metastatic activity in breast and prostate cancers.

They found that the production of Maspin is repressed by a series of events triggered by tumor inflammatory cells, with the result that prostate cancer cells spread.

"An excellent inverse correlation between IKKa activation and Maspin production was detected, such that advanced prostate cancer cells contain high amounts of activated IKKa in their nuclei and express little or no Maspin," said Karin.

He noted that a perfect correlation between nuclear accumulation of activated IKKa and reduced maspin expression was also seen in human prostate cancer, and both correlated with the clinical stage of the disease.

Karin and his colleagues discovered a signaling pathway that increased metastases in a mouse model of prostate cancer. The pathway is activated by a ligand that binds to a Receptor that Activates Nuclear factor Kappa-B (RANK).

RANK ligand has been shown in previous studies to be an important inflammatory protein (cytokine) that can lead to bone loss through activation of bone resorbing cells.

RANK ligand, produced by inflammatory cells that invade advanced prostate tumors, triggers a chain reaction in which IKKa is activated, allowing it to enter the nucleus of the cancer cell, repressing Maspin. IKKa is a key linchpin in the pathway that turns off the Maspin gene and activates the metastatic program.

The new results also support the view that RANK ligand is a general promoter of prostate, and possibly breast, cancer metastasis. "Maspin is a very potent inhibitor of metastasis; in a patient with metastasis, cells have found a way to turn off Maspin, which may depend on invasion of the tumor with RANK ligand-producing cells that activate IKKa," said Karin.

Malignancies progress through stages. In early, non-metastatic tumors, a high level of Maspin is present, but it is turned off in late stages. Early tumors contain low amounts of active nuclear IKKa, whereas late-stage tumors contain the highest levels of active nuclear IKKa.

The researchers also found a striking elevation in expression of RANK ligand in late tumors, but it was not expressed by the cancer cells. Instead, it is expressed by invading inflammatory cells. Interference with RANK ligand production or activation, as well as interference with IKKa activation, may offer new therapeutic strategies for prevention of metastatic disease.


Related medicine news :

1. Inflammation may help battle infection in gums
2. Inflammation Linked to Colon Cancer
3. Bee Venom Effective In Reducing Inflammation
4. Inflammation reduced by consuming oily fish
5. Research Shows Carbon Monoxide Prevents Inflammations
6. ‘Inflammation Gene’ identified by scientit
7. High-Fat Diet Can Ward Off Inflammation In The Gut
8. Inflammation May Indicate Heart Problems
9. Inflammation and WBC count has a link to deaths by cancer
10. Mediterranean Diet Lowers Inflammation Levels In Elderly
11. PET Scans Help In Monitoring Progress of Lung Inflammation
Post Your Comments:

(Date:11/24/2015)... Salt Lake City, UT (PRWEB) , ... November 24, 2015 , ... ... according to Forbes Magazine. For a business, it is critical that the first impression ... of a business, they are not likely to buy anything or want to return. ...
(Date:11/24/2015)... ... November 24, 2015 , ... ... Reactor System. Brillouin is the developer of renewable energy technologies capable of producing ... reactions (“LENR”), announced today that its WET™ and HHT™ Boiler System reactor core ...
(Date:11/24/2015)... Indianapolis, IN (PRWEB) , ... November 24, 2015 ... ... employee benefits advisory organization, is pleased to welcome Winter-Dent & Company as its ... strive from day one to become a client's most trusted advisor regardless of ...
(Date:11/24/2015)... ... November 24, 2015 , ... The American ... support their local poison centers through donations on Tuesday, Dec. 1, 2015. Since ... “a day that inspires people to collaborate in improving their local communities and ...
(Date:11/24/2015)... MI (PRWEB) , ... November 24, 2015 , ... Serenity ... released a series of recent video interviews with some of the staff members at ... at the residential treatment facility, as well as some of the things that make ...
Breaking Medicine News(10 mins):
(Date:11/24/2015)... Nov. 24, 2015 Diplomat Pharmacy, Inc. (NYSE: DPLO) ... of Clinical Services, Education and Human Resources will be presenting ... Oncology Drugs: Health Plan Strategies for a Dynamic Market" on ... Fenrick , a consultant with the Cambridge Advisory Group, where ... The webinar will discuss the rapid growth ...
(Date:11/24/2015)... 2015 iRhythm Technologies, Inc. , a leading digital ... that it will participate in the 27th Annual Piper Jaffray Healthcare ... York, NY . Kevin King , Chief Executive ... 2015 at 8:50am ET. --> ... --> . --> iRhythm is a ...
(Date:11/24/2015)... , November 24, 2015 ... CETP Inhibitors, MTTP Inhibitors, ApoB Inhibitors and PPAR Agonists ... going to grow at the fastest rates? This ... assessing data, trends, opportunities and prospects there. ,  ,Our ... the most lucrative areas in the industry and the ...
Breaking Medicine Technology: