Navigation Links
Lung cancer cells activate inflammation to induce metastasis
Date:12/31/2008

A research team from the University of California, San Diego School of Medicine has identified a protein produced by cancerous lung epithelial cells that enhances metastasis by stimulating the activity of inflammatory cells. Their findings, to be published in the January 1 issue of the journal Nature, explain how advanced cancer cells usurp components of the host innate immune system to generate an inflammatory microenvironment hospitable for the metastatic spread of lung cancer. The discovery could lead to a therapy to limit metastasis of this most common lethal form of cancer.

The scientists headed by Michael Karin, Ph.D., UC San Diego Distinguished Professor of Pharmacology and Pathology, who has been investigating the effects of inflammation on cancer development and progression used a straightforward biochemical approach to identify proteins produced by metastatic cancer cells that are responsible for generation of an inflammatory microenvironment that supports the growth of metastases. Focusing on macrophages, white blood cells that are key players in the immune response to foreign invaders as well as in cancer growth and progression, they screened for factors produced by metastatic cancer cells in mice that could stimulate the activity of this inflammatory cell type.

Among the mouse cell lines screened, a highly metastatic cell line called Lewis lung carcinoma (LLC) showed particularly potent activation of macrophages. Furthermore, macrophage activation was mediated by a secreted protein. Biochemical purification of proteins secreted by LLC cells resulted in identification of an extracellular matrix protein called versican as the major macrophage activator and metastasis enhancing factor. Versican is also found in very low amounts in normal human lung epithelial cells, but is upregulated in human lung cancer, where a very large amount of this protein is found, especially in aggressive tumors.

The scientists found that versican strongly enhances LLC metastatic growth by activating receptors that lead to production of cytokines signaling proteins that regulate the immune system. One of these receptors, TLR2, and a cytokine, TNFα, were found to be required for LLC metastasis. However, the normal function of TLR2 and TNF is in host defense-innate immunity to microbial infections. According to Karin, these findings are relevant, not just to the mouse model, but also to human lung cancer the most common cause of cancer-related deaths worldwide. The major cause of lung cancer is tobacco smoking.

"By usurping these elements of the host immune system, versican helps generate an inflammatory environment that spurs the growth and spread of metastatic cancer," said Karin. "If we can find a way to block the production of versican or its binding to TLR2, therapeutic intervention could be used to limit metastasis of lung cancer."


'/>"/>

Contact: Debra Kain
ddkain@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

Related medicine news :

1. Why prostate cancer patients fail hormone deprivation therapy
2. Few DNA repair genes maintain association with cancer in field synopsis
3. High Insulin May Boost Odds of Breast Cancer
4. Vitamins Fail to Prevent Cancer: Study
5. Errors involving medications common in outpatient cancer treatment
6. Young blood fights cancer
7. Food Phosphates Might Spur Lung Cancer
8. Minimizing obesitys impact on ovarian cancer survival
9. RCOG.com and ProstRcision.com Increase Online Presence for Cancer Information
10. Lung Cancer: Still the Biggest Cancer Killer, by Far
11. Cancer drug effectively treats transplant rejections
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/11/2016)... ... 12, 2016 , ... The Journal of Pain Research has seen ... SJR uses data taken from the Scopus database (Elsevier B.V.) and is a measure ... by the journal over a three year period and also the importance of the ...
(Date:2/11/2016)... ... 11, 2016 , ... The president released a FY 2017 budget request on ... more of the cost burden to military beneficiaries. , MOAA’s president, retired Air ... budget as including limited quantifiable benefit fixes mixed with numerous beneficiary fee hikes. , ...
(Date:2/11/2016)... ... February 11, 2016 , ... Hall Integrative Health and ... for their simultaneous grand openings in March. All seven practices are set to ... wondering, is reversing diabetes possible? According to this 2011 CNN article it is ...
(Date:2/11/2016)... ... 2016 , ... Thermi™, a world leader in thermistor-regulated energy ... promotions of Allison Kelly to executive vice president of the company’s new North ... North American capital sales, and Wendy Oseas to vice president of global marketing. ...
(Date:2/11/2016)... ... 11, 2016 , ... Atlantic Information Services, Inc. (AIS) is ... Case Study for Plans and Purchasers.” Executives from Intel Corp. and Providence Health ... value-based health benefits program Connected Care, will discuss the challenges they faced (and ...
Breaking Medicine News(10 mins):
(Date:2/11/2016)... Ill. , Feb. 11, 2016  AbbVie, ... the AbbVie Rheumatology Scholarship, designed to provide financial ... disease as they pursue higher education goals. Fifteen ... for the 2016-2017 school year. The AbbVie Rheumatology ... Tracie Haas , vice president, corporate social responsibility, ...
(Date:2/11/2016)... Feb. 11, 2016  Community pharmacists can help improve ... the pharmacy through a custom-built medication synchronization program, Cardinal ... and owner at Schieber Family Pharmacy in ... a lot of patients enrolled in this medication synchronization ... a win for the patient, and it,s a win ...
(Date:2/11/2016)... , Feb. 11, 2016 Scientists from ... method that opens the door to genetic analysis ... have been impossible to isolate with 100 percent ... specific tumor types in various stages of development, ... of these cells that are clinically relevant, and ...
Breaking Medicine Technology: