Lung cancer cells activate inflammation to induce metastasis

Dec 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."

Source: University of California - San Diego

Explore further: 3-D human skin maps aid study of relationships between molecules, microbes and environment

Related Stories

Nano packages for anti-cancer drug delivery

Mar 18, 2015

Cancer stem cells are resistant to chemotherapy and consequently tend to remain in the body even after a course of treatment has finished, where they can often trigger cancer recurrence or metastasis. A new ...

Molecular ruler sets bacterial needle length

Mar 16, 2015

When a salmonella bacterium attacks a cell, it uses a nanoscopic needle to inject it with proteins to aid the infection. If the needle is too short, the cell won't be infected. Too long, and the needle breaks. ...

Innovative light therapy reaches deep tumors

Mar 09, 2015

Light long has been used to treat cancer. But phototherapy is only effective where light easily can reach, limiting its use to cancers of the skin and in areas accessible with an endoscope, such as the gastrointestinal ...

New nanodevice defeats drug resistance

Mar 02, 2015

Chemotherapy often shrinks tumors at first, but as cancer cells become resistant to drug treatment, tumors can grow back. A new nanodevice developed by MIT researchers can help overcome that by first blocking ...

3-D printers to make human body parts? It's happening

Feb 04, 2015

It sounds like something from a science fiction plot: So-called three-dimensional printers are being used to fashion prosthetic arms and hands, jaw bones, spinal-cord implants - and one day perhaps even living human body ...

Recommended for you

'Google Maps' for the body: A biomedical revolution

14 hours ago

A world-first UNSW collaboration that uses previously top-secret technology to zoom through the human body down to the level of a single cell could be a game-changer for medicine, an international research ...

New compounds could offer therapy for multitude of diseases

15 hours ago

An international team of more than 18 research groups has demonstrated that the compounds they developed can safely prevent harmful protein aggregation in preliminary tests using animals. The findings raise hope that a new ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

E_L_Earnhardt
1 / 5 (2) Dec 31, 2008
It's "Thermodymic!"! I give cancer to little fish by HEATING their environment above their climitological pattern. I CURE them by going BELOW that temp! Electron speed and spin = heat = accelerated mitosis!

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.