Navigation Links
Inflammation may play role in metastasis of prostate cancer

Many would assume that "mounting an immune response" or "having your body fight the cancer" is a good thing. Now, research at the University of California, San Diego (UCSD) School of Medicine strongly suggests that inflammation associated with the progression of tumors actually plays a key role in the metastasis of prostate cancer.

The research, appearing online March 19 in advance of publication in the journal Nature, identifies a mechanism which triggers metastasis, which is the spread of cancer in late stages of prostate cancer development. The findings by Michael Karin, Ph.D., professor of pharmacology in UCSD's Laboratory of Gene Regulation and Signal Transduction, and colleagues may help solve the puzzle of why it takes so long for cancer to metastasize, as well as what causes it to do so. 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 cou nterproductive," said Gonias.

In research using mouse models and confirmed in human tissue, the scientists observed that a protein kinase called 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 c ells 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.
'"/>

Source:University of California - San Diego


Related biology news :

1. How an AIDS-Related Cancer Unleashes Inflammation
2. Researchers Discover Gene That Determines Asthma Susceptibility By Regulating Inflammation
3. Inflammation and drugs to control this activity studied in a variety of tumors sites
4. Inflammation markers identify fatigue in breast cancer survivors
5. 3-D model reveals secrets of metastasis
6. Two-faced protein can stop metastasis or promote it, researchers say
7. Newly discovered behavior in cancer cells signals dangerous metastasis
8. Trojan Horse agent halts bone metastasis in mice
9. Genes set scene for metastasis
10. Mitochondrial DNA mutations play significant role in prostate cancer
11. Weizmann Institute scientists develop a new approach for directing treatment to metastasized prostate cancer in the bones.

Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/5/2017)... 5, 2017  The Allen Institute for Cell Science ... a one-of-a-kind portal and dynamic digital window into the ... the first application of deep learning to create predictive ... lines and a growing suite of powerful tools. The ... and future publicly available resources created and shared by ...
(Date:4/4/2017)... April 4, 2017   EyeLock LLC , a ... the United States Patent and Trademark Office (USPTO) has ... the linking of an iris image with a face ... represents the company,s 45 th issued patent. ... very timely given the multi-modal biometric capabilities that have ...
(Date:3/30/2017)... KONG , March 30, 2017 The ... a system for three-dimensional (3D) fingerprint identification by adopting ground breaking ... into a new realm of speed and accuracy for use in ... at an affordable cost. ... ...
Breaking Biology News(10 mins):
(Date:7/17/2017)... , ... July 17, 2017 , ... ... company that has developed and intends both to manufacture and sell reagents used ... the NASDAQ Capital Market. , Headquartered in Sandy, Utah, Co-Diagnostics’ intellectual property and ...
(Date:7/16/2017)... (PRWEB) , ... July 16, 2017 , ... ... equipment and analytical instruments announced the launch of its new line of Rocking ... five rocking and waving shaker models (both analog and digital) for laboratory applications ...
(Date:7/15/2017)... ... July 15, 2017 , ... Cuvette manufacturer ... During this time, the people at FFS have learned that their biggest asset ... at FFS are able to launch new products to meet the changing needs of ...
(Date:7/14/2017)... ... ... Dr. Joshua Mondlick has introduced the LANAP® protocol to treat gum disease ... the Phoenix area. Dr. Mondlick is at the forefront of the future of ... re-grow bone and with significantly less pain than traditional surgery options. , “With traditional ...
Breaking Biology Technology: