Navigation Links
Molecular Cause of Breast Cancer Metastasis Discovered
Date:4/3/2008

Signaling events in tumor pave the way for lung invasion, study shows

THURSDAY, April 3 (HealthDay News) -- Certain cancers tend to spread to specific tissues, and now researchers have gained a molecular handle on how that happens.

Working with breast tumors, Joan Massague, chairman of the Cancer Biology and Genetics Program at Memorial Sloan-Kettering Cancer Center in New York City, and his colleagues discovered a signaling "relay" that enables the cancer to molecularly "soften" its target tissue -- the lung in this case -- allowing circulating breast cancer cells to pass through capillary walls and penetrate the lung.

"It provides a very nice mechanism for how breast cancer cells specifically get out of the circulation and into the lungs. Nobody knew how they did that before," said Karl Saxe, a scientific program director at the American Cancer Society.

The results were published in the April 4 issue of Cell.

Key to this study is a signaling molecule called TGF-beta. Early in cancer progression, TGF-beta acts as a tumor suppressor, inhibiting cancer growth. Later, it actually stimulates cancer progression and metastasis. Massague was interested in how tumors trigger this molecular dichotomy.

His team began by identifying a molecular signature, a pattern of gene expression of 153 genes that identifies tumors that are both expressing and responding to TGF-beta. They then applied that signature to hundreds of primary breast tumors.

While there was no apparent correlation between TGF-beta signaling and metastasis in breast cancers that also express the estrogen receptor, the team found that tumors that were estrogen receptor-negative were much more likely to metastasize to lung. No similar correlation was found for metastasis to the bone, liver or brain.

When the team then asked which of the genes in the signature was responsible for this selectivity, they identified a second element in the relay, a signaling molecule called angiopoietin-like 4 (ANGPTL4), whose expression is induced by TGF-beta. ANGPTL4 disrupts capillary walls, loosening the connections between adjacent cells and allowing the metastasizing cells to "seed" the tissue.

Disrupt TGF-beta signaling, or ANGPTL4 expression, and lung metastasis is disrupted, the researchers found. Enhance that signaling, and lung metastasis is increased.

"This is a molecular and biological explanation of why and how responding to TGF-beta contributes to lung metastasis," concluded Massague.

This study also suggests anticancer therapies based on both TGF-beta (which are currently in development) and ANGPTL4 could be useful against metastatic breast cancer, he added.

According to Saxe, the observation that cancers have a way to select targets to spread to is not surprising. "Something like this had to be going on," he said. "But what is very nice and satisfying is to find a very clear mechanism like this to explain why some kinds of breast cell tumors metastasize to the bone and some to lung."

Massague said the reason ANGPTL4 helps cells colonize the lungs but not the bone has to do with the different architecture of the two tissues. Lung tissue is highly vascularized, yet capillaries present a relatively impenetrable barrier to metastasizing cells. Bone, on the other hand, is different, Massague explained, because "they [cancer cells] have windows, because every day in the bone marrow, the capillaries have to let cells in and out."

Similar molecular discriminators may turn out to play a role in a variety of tumors, Saxe said. TGF-beta signaling in general, and ANGPTL4 in particular, may control metastasis in a variety of tumor types. Other signaling pathways could also be involved, and Saxe said he expects this study will spark new research to investigate those possibilities.

As Dr. Kornelia Polyak, a researcher with the Breast Cancer Genetics Lab at Harvard Medical School, pointed out, metastasis likely involves "an orchestra of genes that together can contribute to different steps" of the process. "It's likely to be a combination of genes, and this particular one [ANGPTL4] is one of them."

More information

For more on breast cancer, visit the National Cancer Institute.



SOURCES: Joan Massague, Ph.D., chairman, Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York City, and investigator, Howard Hughes Medical Institute, Chevy Chase, Md.; Charles "Karl" Saxe, Ph.D., scientific program director, extramural research department, American Cancer Society; Kornelia Polyak, M.D., Ph.D., researcher, Breast Cancer Genetics Lab, and associate professor, medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston; April 4, 2008, Cell


'/>"/>
Copyright©2008 ScoutNews,LLC.
All rights reserved  

Related medicine news :

1. A new molecular zip code, and a new drug target for Huntingtons disease
2. New knock-out gene model provides molecular clues to breast cancer
3. Molecular probe paints cancer cells in living animals, Stanford researchers find
4. Story ideas from molecular & cellular proteomics
5. SNM seeks novel approaches to molecular imaging to showcase at annual meeting
6. SNM seeks novel approaches to molecular imaging to showcase at annual meeting
7. Molecular fingerprint of breast-cancer drug resistance can predict response to treatment
8. Molecular profiling can accurately predict survival in colon cancer patients
9. Xceed Molecular Names Fran Tuttle to Its Board of Trustees
10. Virginia G. Piper Charitable Trust and Flinn Foundation launch molecular diagnostics initiative
11. Xceed Molecular Launches Ziplex(R) Automated Gene-Expression System at the Association for Molecular Pathology, Booth 84/85
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Molecular Cause of Breast Cancer Metastasis Discovered
(Date:10/13/2017)... ... October 13, 2017 , ... Global Healthcare Management’s 4th Annual Kids Fun Run ... This free event, sponsored by Global Healthcare Management’s CEO, Jon Letko, is aimed ... geared towards children of all ages; it is a non-competitive, non-timed event, which is ...
(Date:10/13/2017)... ... October 13, 2017 , ... “America On The Brink”: the ... “America On The Brink” is the creation of published author, William Nowers. Captain ... As a WWII veteran, he spent thirty years in the Navy. Following his ...
(Date:10/12/2017)... ... October 12, 2017 , ... IsoComforter, Inc. ( https://isocomforter.com ), one ... an innovative new design of the shoulder pad. The shoulder pad provides optimal ... controlling your pain while using cold therapy. By utilizing ice and water that is ...
(Date:10/12/2017)... PA (PRWEB) , ... October 12, 2017 , ... ... is the recipient of a 2017 Folio Magazine Eddie Digital Award for ‘Best B-to-B ... York City on October 11, 2017. , The annual award competition recognizes editorial and ...
(Date:10/12/2017)... (PRWEB) , ... October 12, 2017 , ... ... of $3,296 in property taxes a year. In some states—like New York, New ... , By contrast, many overseas retirement havens have extremely low property-tax rates, which ...
Breaking Medicine News(10 mins):
(Date:10/11/2017)... 11, 2017  Caris Life Sciences ® , a ... promise of precision medicine, today announced that St. Jude ... Oncology Alliance™ (POA) as its 17 th member. ... Jude Crosson Cancer Institute will help develop standards of ... tumor profiling, making cancer treatment more precise and effective. ...
(Date:10/7/2017)... , Oct. 6, 2017   Provista, ... more than $100 billion in purchasing power, today announced ... and information. The Newsroom is the online ... industry trends, infographics, expert bios, news releases, slideshows and ... access to a wealth of resources at their fingertips, ...
(Date:10/2/2017)... 2, 2017 Diplomat Pharmacy, Inc. (NYSE: ... and Consulting, LLC , and named its founder as ... in Tennessee , will operate under ... EnvoyHealth,s service offerings for health care partners to include ... "In an interoperable world, technology delivers ...
Breaking Medicine Technology: