New form of cell death discovered.

[Guest guest]

http://sciencenow.sciencemag

<http://sciencenow.sciencemag.org/cgi/content/full/2007/1129/4?rss=1>

..org/cgi/content/full/2007/1129/4?rss=1

" " Scientists have discovered a novel form of cell death in which cells

crawl inside other cells to die. The process, dubbed entosis, may be a

method of suppressing tumors " "

" " Craig , a cancer biologist at the University of Pennsylvania,

is more skeptical. The fact that some cells survive entosis, he says,

suggests that it is not a very effective process for suppressing tumors

and raises concern that it may be a phenomenon that primarily occurs in

the lab rather than in the body. " "

New Form of Cell Death Discovered

By Steve

ScienceNOW Daily News

29 November 2007

Scientists have discovered a novel form of cell death in which cells

crawl inside other cells to die. The process, dubbed entosis, may be a

method of suppressing tumors, the researchers say, but others aren't so

sure.

For more than 25 years, scientists examining cultures of human cancer

cells have occasionally spotted cells tucked within other cells. But the

phenomenon remained largely unexplored until a team led by cell

biologist Overholtzer of Harvard Medical School in Boston

recently saw the same thing while working with a line of normal breast

cells. As in breast tissue, these cultured cells usually grow on a

membrane or matrix. When they became detached, however, some cells

appeared to be enveloped by other cells. Intrigued, the researchers

looked closer.

Overholtzer's team found that up to 70% of the detached cells died once

engulfed by another detached cell. However, up to 9% divided while

enveloped and up to 18% were eventually released unharmed. Blocking the

mechanisms involved in other methods of cell death including apoptosis

and phagocytosis did not disrupt the process, confirming that entosis

operates in a different way.

Further experiments revealed that cadherins, proteins that keep cells

joined to each other, are required for entosis. The researchers are

still working out the details, but they speculate in the 30 November

issue of Cell that entosis occurs due to an imbalance in adhesion forces

between two cells when they dislodge from the matrix. This could lead to

one cell pushing into the other until it is engulfed, akin to pressing

your fist into a balloon.

However entosis occurs, it appears to be widespread. The team found

evidence of the process in several other cell types, including breast,

ovarian, umbilical cord, and kidney cancer cells. Overholtzer says tumor

suppression may be one function of entosis. When a chemical that

inhibits entosis was applied to a line of breast cancer cells, colony

formation--an indicator of tumor growth in vitro--increased 10-fold.

Conversely, cancer cells could be using entosis as a survival tool. It

may be " a way for a tumor cell to escape recognition by chemotherapeutic

drugs or the immune system " by hiding out inside another cell, says

Maureen , a molecular biologist at Fox Chase Cancer Center in

Philadelphia, Pennsylvania. That may explain why not all cells die

during entosis.

Craig , a cancer biologist at the University of Pennsylvania, is

more skeptical. The fact that some cells survive entosis, he says,

suggests that it is not a very effective process for suppressing tumors

and raises concern that it may be a phenomenon that primarily occurs in

the lab rather than in the body.

Zavie (age 69)

67 Shoreham Avenue

Ottawa, Canada, K2G 3X3

dxd AUG/99

INF OCT/99 to FEB/00, CHF

No meds FEB/00 to JAN/01

Gleevec since MAR/27/01 (400 mg)

CCR SEP/01. #102 in Zero Club

2.8 log reduction Sep/05

3.0 log reduction Jan/06

2.9 log reduction Feb/07

3.2 log reduction Jun/07

3.6 log reduction Sep/07

e-mail: zmiller@...

Tel: 613-726-1117

Fax: 309-296-0807

Cell: 613-202-0204

ID: zaviem