Pioneering study looks at p53's role in tumor-stroma interactions

October 25, 2006

Atlanta, GA-Researchers at Emory University's Winship Cancer Institute have conducted the first comprehensive study of the role an important tumor suppressor gene plays in cancer development.

P53 is known as a major tumor suppressor that is frequently mutated in human cancer. In this study, researchers used novel proteomic techniques to identify the proteins secreted by cells specifically in response to p53. The findings suggest a newfound role for wt-p53 in the control of the tumor's ability to communicate with the normal stromal cells surrounding it. The results of the study, "Proteomic identification of the wt-p53-regulated tumor cell secretome," are found in the October 9 advance online print of Oncogene.

"Cancer formation is traditionally thought of as a cell-autonomous process driven by mutations in genes that increase cell proliferation and survival, where a tumor is composed primarily of transformed cells," says Erwin G. Van Meir, PhD, Professor of Neurosurgery and Hematology/Oncology and lead-author of the study. "But increasing evidence suggests that the tumor microenvironment also contributes to neoplasm and that tumor-stroma interactions play a major role in tumor development, maintenance, and progression. A tumor is more like a casserole of chili than a bowl of white rice, where all the components in the mix interact. We need to better understand these tumor-stroma interactions to develop more effective cancer therapies."

But little is know about how the genetic changes that underlie cell transformation elicit extrinsic changes that modulate cell interactions. So, the researchers examined whether those events involve a modification in the cell's secreted proteins, which then act as mediators of intercellular communication.

Focusing on p53 as a proof-of-principle was a natural starting point as p53 is a transcription factor that directly controls the synthesis of numerous proteins. p53 is best known for its role in maintaining genomic integrity and cell survival in response to DNA damage. Yet some prior studies suggested that p53 could influence the tumor microenvironment by suppressing angiogenesis and tumor invasion.

To identify p53-regulated secreted proteins involved in intercellular communication, the researchers used a cell line derived from a malignant human glioma. The researchers found a total of 111 secreted proteins, 39 that showed enhanced secretion and 21 that showed inhibited secretion in response to wt-p53 expression. However, none of the proteins were found to be transcriptional targets, which suggests that wt-p53 may have an indirect role in intracellular protein trafficking and secreted-protein stability, says Dr. Van Meir. "These secreted targets will be helpful in better understanding how wt-p53 may modulate interactions of tumor cells with their environment and establishes p53 loss in tumors as a major trigger of changes in tumor-stroma interactions. A better understanding of these phenomena will improve our ability to devise new therapies for cancer."
-end-
The study was funded by the American Brain Tumor Association, the Pediatric Brain Tumor Foundation of the US, the National Institutes of Health, and the National Science Foundation. The team of researchers included Winship Cancer Institute and Emory University School of Medicine's Dr Erwin G. Van Meir, Fatima W. Khwaja, Ph.D., Paul Svoboda, Ph.D., Matthew Reed, Ph.D., Jan Pohl and Beata Pyrzynska, Ph.D.

Emory University Health Sciences Center

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.