Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Growth of common skin cancer blocked in gene-switch mice

29.12.2004


Scientists have identified genes that promote the growth and recurrence of skin cancer

Dr. Andrzej Dlugosz and colleagues at the University of Michigan and the National Cancer Institute have examined the functions of the Hedgehog (Hh) signaling pathway in basal cell carcinoma, the most common form of cancer, and have uncovered a subset of tumor cells that are resistant to inhibition of the Hh pathway. This new finding has important implications for the treatment of this widespread disease.

Their report is being released online tomorrow, in advance of its January 15th publication date by the journal Genes & Development http://www.genesdev.org/cgi/doi/10.1101/gad.1258705).



Basal cell carcinoma (BCC) affects over 1,000,000 Americans each year and frequently arises on sun-exposed sites such as the face. Surgical removal of BCCs is an effective approach to treating these cancers, which generally have a slow growth rate and seldom metastasize. However, untreated BCCs can cause extensive local tissue damage, and surgical procedures can produce significant scarring in cosmetically sensitive locations such as the face.

The Hh signaling pathway plays a key role in normal development, and its dysfunction has been implicated in a number of different human diseases and neoplasms, including BCCs in skin and cancers arising in brain, lung, prostate, pancreas and other gastrointestinal organs. Dr. Dlugosz and colleagues focused on the function of uncontrolled Hh pathway signaling in the growth of BCC.
The investigators used genetically engineered mice in which they could manipulate expression of a Hh pathway component, called Gli2, effectively turning it on or off at will in the skin. As expected, expression of Gli2 resulted in BCC formation. In addition, the researchers found that sustained expression of Gli2 is necessary for the continued growth of these tumors. When Dr. Dlugosz and colleagues turned Gli2 off, the BCC tumor cells stopped growing and were eliminated via execution of a programmed cell death process. These results are consistent with previous work from other labs studying different Hh-associated tumors, "but we were very surprised to see that some tumor cells persisted after shutting down Gli2 expression," said Dr. Dlugosz.

In some of the regressed tumors Gli2 reactivation leads to resumption of BCC tumor growth, suggesting that the residual cell population may represent BCC tumor stem cells, but Dr. Dlugosz cautions that there is as yet no definitive evidence that tumor stem cells exist in BCC. In additional studies, the researchers found that regressing BCC cells could be reprogrammed to differentiate into various epithelial cell types, ultimately capable of assembling fully-formed hair follicles. These results suggest that BCCs contain cells capable of multi-lineage differentiation, similar to normal hair follicle stem cells from which they may arise.

If the results of this study are applicable to human BCC, the discovery of residual tumor cells and tumor recurrence may be particularly important given the current efforts to develop Hh pathway inhibitors as a means of combating human BCCs as well as other cancers. In contrast to other cancer models where inhibition of Hh signaling leads to durable tumor regression, Dr. Dlugosz’s new work raises the possibility that Hh pathway inhibition in BCCs, while effectively diminishing tumor size, may not be curative due to the survival of this residual tumor cell population.

Nevertheless, "our work demonstrates that BCC growth in this model remains strictly dependent on the Hh pathway," says Dr. Mark Hutchin, lead author on the paper. This is different from many other genetic mouse models of cancer, in which tumor regression following inhibition of an oncogene is frequently followed by the emergence of malignancies that have activated alternative cancer-causing pathways. The fact that this does not happen in regressed mouse BCCs suggests that any residual human BCC cells, if present, should also remain in check as long as the Hh pathway is effectively inhibited.

Heather Cosel | EurekAlert!
Further information:
http://www.cshl.edu
http://www.genesdev.org/cgi/doi/10.1101/gad.1258705

More articles from Life Sciences:

nachricht Closing in on advanced prostate cancer
13.12.2017 | Institute for Research in Biomedicine (IRB Barcelona)

nachricht Visualizing single molecules in whole cells with a new spin
13.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

A whole-body approach to understanding chemosensory cells

13.12.2017 | Health and Medicine

Water without windows: Capturing water vapor inside an electron microscope

13.12.2017 | Physics and Astronomy

Cellular Self-Digestion Process Triggers Autoimmune Disease

13.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>