Nav: Home

Cancer genes and the tumor milieu

July 08, 2019

The tumor microenvironment (TME) is a mix of fluids, immune cells and blood vessels which envelops the tumors. Interactions between tumor cells and the TME determine the progression and fate of tumors. Therefore, understanding the composition and functions of the TME is thus very important for keeping cancer in check. Although several genetic mutations can result in the incidence of cancer, not much is known about their effects on the TME. A research team led by Chiaki Takahashi at Kanazawa University has recently reported the role of one such cancer gene, RB, in this regard.

Retinoblastoma (RB) is a tumor-suppressing gene, mutations in which promote the growth of tumors. Therefore, the team first inactivated RB in mice with sarcoma, a type of cancer, and observed the ensuing effects on tumor growth. The tumors in these mice were indeed enlarged. Further analysis of their TME revealed the presence of new blood vessels which usually nourish cancer cells. Newly recruited immunosuppressive cells, which overpower the body's natural defense system, were also found in the TME. Inactivation of RB thus made the TME conducive for cancer progression.

The researchers then dug deeper to investigate molecular changes in the TME. The secretion of Ccl2, a molecule that attracts immunosuppressive cells, was found to be greatly increased. Alterations in the TME, however, were not seen in mice without the Ccl2 gene, suggesting its increase as the primary culprit for the RB-mediated TME changes. To establish the relevance of these findings to human cancer, breast cancer cell lines were used. As expected, enhanced secretion of Ccl2 was also observed in the breast tumor cells with inactivated RB. In previous reports, the research team has disclosed imbalances in certain mitochondrial metabolites in RB-associated cancer. Mitochondrial superoxide (MS) is one such metabolite. To build on those findings, they examined whether altered Ccl2 secretion was related to MS imbalance in RB-associated cancer. When breast cancer cells were treated with antioxidants, which prevent the accumulation of MS, Ccl2 secretion was greatly decreased. The two were thus closely linked.

This study elucidated detailed mechanisms by which mutations in the RB gene induce changes in the TME and promote tumor growth. A deeper understanding of this dynamic will help devise tumor-suppressing strategies in cancer patients with RB mutations. Preventing mitochondrial imbalances or directly targeting Ccl2 in the TME of such patients warrant further investigation as therapeutic approaches.
-end-


Kanazawa 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

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

In & Out Of Love
We think of love as a mysterious, unknowable force. Something that happens to us. But what if we could control it? This hour, TED speakers on whether we can decide to fall in — and out of — love. Guests include writer Mandy Len Catron, biological anthropologist Helen Fisher, musician Dessa, One Love CEO Katie Hood, and psychologist Guy Winch.
Now Playing: Science for the People

#543 Give a Nerd a Gift
Yup, you guessed it... it's Science for the People's annual holiday episode that helps you figure out what sciency books and gifts to get that special nerd on your list. Or maybe you're looking to build up your reading list for the holiday break and a geeky Christmas sweater to wear to an upcoming party. Returning are pop-science power-readers John Dupuis and Joanne Manaster to dish on the best science books they read this past year. And Rachelle Saunders and Bethany Brookshire squee in delight over some truly delightful science-themed non-book objects for those whose bookshelves are already full. Since...
Now Playing: Radiolab

An Announcement from Radiolab