Nav: Home

Family dynamics: Molecules from the same family have different effects in cancer prognosis

May 13, 2019

Researchers at Hiroshima University have found that different levels of two molecules of the same family--TIMP-1 and TIMP-4--can influence prognosis of liposarcoma.

High levels of TIMP-1 lead to a poor prognosis while high TIMP-4 indicates a less severe form of liposarcoma. This study, published in Carcinogenesis 10th May 2019, described the molecules' mechanism of action through the YAP/TAZ pathway. Further research can lead to new treatments and better methods of diagnosis for liposarcoma.

Different types of cancer have different prognoses (medical outcomes) and some are easier to treat than others. Liposarcoma is a cancer that affects fat cells and generally comes in 2 types: well-differentiated and dedifferentiated. The well-differentiated type resembles normal fat cells while the dedifferentiated tumors have areas that do not resemble fat cells. This makes dedifferentiated more difficult to treat and, even after treatment, can reoccur about 80% of the time. Currently doctors have to rely on standard treatments such as chemotherapy, radiation and surgery, which are not very effective for aggressive liposarcoma.

TIMP (Tissue Inhibitor of Metalloproteinases) is a family of molecules that have been observed to have varying effects in different types of cancer. These molecules stop enzymes in a cell that degrade metalloproteins, which make up a part of the environment outside a cell. This environment keeps cells in place and makes it harder for them to move to other tissues. Assistant Professor Toshinori Ando (a member of the study group at Hiroshima University and currently at the University of California, San Diego) describes it as a "mesh" that you can't easily move through.

"But once metalloproteinases [are] released from you [they] can cut through the mesh then make a road to the other side." explains Ando.

Understanding this mechanism leads to the conclusion that TIMP expression is unfavorable to the cancer cell, as it stops the enzyme creating this road through the "mesh". However, previous research revealed that one of the members of this family: TIMP-1 was highly expressed in various types of cancer including breast, pancreatic and brain cancer. Previous study by the research team at Hiroshima University found that TIMP-1 works as a promotor of tumor proliferation in many cancers.

Conversely, TIMP-4 presence was observed in normal fat cells and in the well-differentiated type of liposarcoma, leading the research team to conclude that the two molecules have opposite effects in liposarcoma aggressiveness. How they operated was poorly understood before this new study, according to Ando.

The research group observed cells grown from liposarcoma tissue; how they moved and replicated. Cells with high levels of TIMP-1 showed more proliferation and migration, while the opposite was true for TIMP-4. The mechanism behind the molecules' behavior in liposarcoma is the activation or suppression of a pathway that is important for cell proliferation: the YAP/TAZ pathway. YAP/TAZ are proteins that promote cell proliferation and are activated in liposarcoma, especially in dedifferentiated type. TIMP-1 activates this pathway, which leads to tumor growth and spread, while TIMP-4 suppresses the pathway. In this study, the research team showed TIMP-1 promotes dedifferentiated liposarcoma cell proliferation through the YAP/TAZ pathway.

Understanding this mechanism can lead to new therapeutics, such as targeting TIMP-1 or increasing the amount of TIMP-4 in the cancer cells, speculates Ando. As these two molecules are present in the blood of cancer patients Ando also thinks that detecting the levels of these molecules can be helpful for predicting patient survival alongside diagnosis by biopsy.
-end-
Since its foundation in 1949, Hiroshima University has strived to become one of the most prominent and comprehensive universities in Japan for the promotion and development of scholarship and education. Consisting of 12 schools and 11 graduate schools, ranging from International Development and Cooperation to Integrated Arts and Sciences, the university has grown into one of the most distinguished research universities in Japan. English website: https://www.hiroshima-u.ac.jp/en

Hiroshima University

Related Cancer Articles:

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.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
More Cancer News and Cancer Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.