Cells united against cancer

August 27, 2007

Sheets of highly organized epithelial cells line all the cavities and free surfaces of the body, forming barriers that control the movement of liquids and cells in the body organs. The organized structure of normal breast epithelial cells may also serve as a barrier against cancer, according to a study by University of Helsinki scientists. The work appears this week in the online edition of the Proceedings of the National Academy of Sciences (PNAS).

Finnish researchers found that the tightly organized architecture of mammary epithelial cells is a powerful restraint against the cancer gene provoked inappropriate proliferation. Their study also links function of a tumor suppressor gene to the development of cancer gene resistant epithelial organization.

"Rogue cancer genes can force epithelial cells to proliferate and proliferation of malignant cells will certainly disrupt the organized epithelial structure. However, there has always been this chicken or the egg problem: Does cancer gene initiate cell proliferation, which causes disruption of the epithelial structure or does loss of tissue structure come first, creating suitable environment for cancer genes to enforce the cell cycle progression"" explains the research team leader Juha Klefstrom, Ph.D. The present study supports the idea that loss of tissue structure comes first.

Experiments with fly models have shown that loss of epithelial organization can enhance the tumorigenic potential of cancer genes (oncogenes) and these findings prompted Juha Klefstrom's team to explore whether the formation of epithelial organization works other way around and suppresses oncogene function. "We were amazed to find out that the formation of organized mammary epithelial architecture in three-dimensional organotypic cell culture correlated with complete loss of oncogenic activities of c-Myc cancer gene" says Klefstrom.

Johanna Partanen, a graduate student in Klefstrom's laboratory and lead author in the article, continues "We also asked how to dismantle the proliferation resistance of the epithelial organization. To find clues to genes involved in the development of organized epithelial structure, we turned back to fly". Epithelial cells of both flies and humans live their lives in the companionship of others, held together by tight belt of adhesion proteins and interactions with supporting extracellular matrix. Developmental geneticists working with fly models have identified an important group of genes, PAR genes, which regulate the development of highly ordered epithelial cell organization. "Most interesting candidate for us was LKB1, the human homologue of Par4 protein, because this gene has strong connection to human epithelial disorders" says Partanen. Previous research done by Akseli Hemminki, Lauri Aaltonen and Tomi Mäkelä at the University of Helsinki has linked this gene to Peutz-Jeghers cancer predisposition syndrome and it has also been suggested that LKB1 has tumor suppressor functions in several epithelial cancers. Klefstrom's team found that epithelial cells missing the LKB1 protein are able to form only cancer-like disorganized epithelial structures. This disorganized environment enables c-Myc oncogene to drive inappropriate cell proliferation.

The study demonstrates that organized epithelial structure can suppress malignant actions of cancer genes and identifies LKB1 tumor suppressor gene as an architect of this proliferation resistant organizational plan. The ordered structure of epithelial cells is frequently lost in epithelial tumors, like breast carcinoma, and the study suggests that loss of structure may play more active role in progression of tumors than previously anticipated.
-end-
This study was funded by the Academy of Finland, Finnish Funding Agency for Technology and Innovation (TEKES), the Sigrid Juselius Foundation, Helsinki University Central Hospital, the Lilly Foundation, and the Juliana von Wendt Foundation.

Johanna I. Partanen, Anni I. Nieminen, Tomi P. Mäkelä and Juha Klefström, PNAS, August 2007 (Early Edition online)

University of Helsinki

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.