Navigation Links
Dormant cancer cells rely on cellular self-cannibalization to survive
Date:1/2/2009

HOUSTON A single tumor-suppressing gene is a key to understanding, and perhaps killing, dormant ovarian cancer cells that persist after initial treatment only to reawaken years later, researchers at The University of Texas M. D. Anderson Cancer Center report in the December Journal of Clinical Investigation.

The team found that expression of a gene called ARHI acts as a switch for autophagy, or self-cannibalization, in ovarian cancer cells. Often a mechanism for cancer cell death, in this case "self-eating" acts as a survival mechanism for dormant cancer cells.

"Prolonged autophagy is lethal to cancer cells, but a little autophagy can help dormant cancer cells survive, possibly by avoiding starvation," said senior author Robert Bast, M.D., vice president for translational research at M. D. Anderson.

"Dormant cells are a major problem in ovarian cancer, breast cancer and other malignancies," Bast said. "We often see ovarian cancer removed, leaving no remaining sign of disease. After two or three years, the cancer grows back. If any remaining cancer cells had continued to grow normally, the disease should have returned in weeks or months.

"So the assumption is that some cells remain dormant without dividing and without developing a blood supply, but the mechanism for this has not been well understood," Bast said.

Bast and colleagues focused on ARHI, short for aplasia Ras homolog member I, a gene found in normal cells, but that is underexpressed in 60-70 percent of ovarian cancers.

When normal levels of ARHI were restored to ovarian cancer cells in the laboratory, autophagy was induced and cancer cells died within a few days.

When the experiments moved to human ovarian cancer grafts in mice, a different effect was noted. ARHI stopped tumor growth and induced autophagy, but did not kill the cancer cells. When ARHI was turned off at 4 to 6 weeks, the ovarian cancer cells grew rapidly.

"Cancer cells had remained viable during ARHI-induced growth arrest and autophagy, which is consistent with a dormant state," Bast said. "When we blocked autophagy with chloroquine, a drug also used to treat malaria, regrowth of the cancers was inhibited, suggesting that autophagy had helped the cancer cells to survive in the absence of a blood supply."

Autophagy is a cellular survival mechanism that protects cells in a variety of ways. In the case of stress caused by lack of nutrients, autophagy is roughly comparable to a person burning body fat to survive the absence of food.

Several protein survival factors were detected within the microenvironment of the ovarian cancer grafts that could prevent autophagy-induced death of ovarian cancer cells in the laboratory. Blocking these survival factors could provide a novel strategy for eliminating dormant ovarian cancer cells and curing more patients.

Whether cancer cells die an autophagic death, remain dormant or exit dormancy to grow again depends on the balance between ARHI's tumor-suppressing activity and the anti-autophagic and proliferative activity of these environmental survival factors, the authors note.

The ARHI-autophagy pathway also provides an inducible model for tumor dormancy. Lack of a model has hindered understanding of dormant cells and the development of treatments to eliminate them, Bast noted.


'/>"/>

Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

Related medicine news :

1. Immune system can drive cancers into dormant state
2. Dormant stem cells for emergencies
3. Conventional prognostic factors fail to explain better prostate cancer survival in most Asian men
4. Survival differences by race most apparent in advanced stages of breast cancer
5. MRI finds breast cancer before it becomes dangerous
6. Investigators uncover intriguing clues to why persistent acid reflux sometimes turns into cancer
7. Pathway links inflammation, angiogenesis and breast cancer
8. Radiologists encouraged to look beyond cancer for clinically unseen diseases
9. Diet high in meat, fat and refined grains linked to risk for colon cancer recurrence, death
10. Immune deficiency linked to a type of eye cancer
11. Drop in breast cancer incidence linked to hormone use, not mammograms
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Dormant cancer cells rely on cellular self-cannibalization to survive
(Date:10/13/2017)... ... October 13, 2017 , ... ... certification process to promote standards of excellence for the field of eating disorders, ... March 22 – 25, 2018 in Orlando, Florida at the Omni Resort at ...
(Date:10/13/2017)... ... October 13, 2017 , ... Southern ... and Jennifer Huggins, PharmD ’17, along with clinical associate professor Janice Frueh, ... cardiovascular diseases during the 15th Annual Women’s Health Conference. The SIU School ...
(Date:10/13/2017)... ... October 13, 2017 , ... Apple Rehab Shelton Lakes ... a mock evacuation of the facility as part of a disaster drill on October ... Hose EMS and Shelton City Emergency Manager, as well as the Connecticut Long ...
(Date:10/13/2017)... , ... October 13, 2017 , ... The Visiting Nurse ... Market. Featuring a collection of specialty vendors and unique items from across the nation, ... quality-focused health and wellness services offered by the VNA. The boutique will be ...
(Date:10/13/2017)... ... ... Global Healthcare Management’s 4th Annual Kids Fun Run brought out many kids this ... by Global Healthcare Management’s CEO, Jon Letko, is aimed at getting kids excited about ... ages; it is a non-competitive, non-timed event, which is all about having fun and ...
Breaking Medicine News(10 mins):
(Date:9/25/2017)... , Sept. 25, 2017  EpiVax, Inc., ... vaccine design, and immune-engineering today announced the launch ... the development of personalized therapeutic cancer vaccines. EpiVax ... provided exclusive access to enabling technologies to the ... MBA will lead EpiVax Oncology as Chief Executive ...
(Date:9/22/2017)... AVACEN Medical (AVACEN) announced that its CE-Marked ... those with the widespread pain associated with fibromyalgia in ... Essex, England commented, "I had ... no sleep at all, tremendous pain, with every movement ... [the AVACEN 100] enough, how this has and is ...
(Date:9/18/2017)... Mich. , Sept. 18, 2017  PMD Healthcare ... Specialty Pharmacy of Kalamazoo, Mich. , ... hub service that expedites and streamlines patient and provider ... PD 2.0, and wellness management services.  ... device used to measure lung function for a variety ...
Breaking Medicine Technology: