From: Subject: OHSU study says stem cell 'fusion' occurs in tumors Date: Sat, 13 May 2006 13:22:22 +0200 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01C67690.4487B370" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.2869 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01C67690.4487B370 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.eurekalert.org/pub_releases/2006-05/ohs-oss050906.php OHSU study says stem cell 'fusion' occurs in = tumors

Public = release date:=20 9-May-2006
[ | E-mail Article ]

Contact: Jonathan Modie
modiej@ohsu.edu
503-494-8231
Oregon Health & = Science=20 University

OHSU study says stem cell 'fusion' occurs in = tumors

PORTLAND, Ore. - An Oregon Health & = Science=20 University study is adding credence to an increasingly popular theory = that=20 fusion is what bonds stem cells with bone marrow cells to regenerate = organ=20 tissue.=20

Scientists in the OHSU School of Medicine found that transplanted = cells=20 derived from adult bone marrow can fuse with intestinal stem cells of = both=20 normal and diseased tissue comprising the cellular lining of intestinal = walls,=20 known as the epithelium. The findings, reported recently in the = Proceedings of=20 the National Academy of Sciences, point to the integral role of bone=20 marrow-derived cells in not only regeneration of damaged tissue, but = also=20 disease progression.=20

"It's the first observation that there's fusion at the level of stem = cells,"=20 said the study's corresponding author, Melissa Wong, Ph.D., assistant = professor=20 of dermatology, and cell and developmental biology. "Second, we're = seeing cell=20 fusion in tumors and we believe that this concept is an underappreciated = mechanism for promoting tumor growth. Our findings have implications on = how=20 tissues regenerate and how, in the process of this regeneration, cells = may=20 become prone to future problems. "=20

Although the tumor in her study did not "initiate" tumors or become=20 malignant, Wong believes the fusion process is one explanation for how = tumors=20 acquire genetic instability and have the potential to give rise to = malignant=20 cancer.=20

One promising result could be in better understanding the careful = balance=20 between rapid and effective regeneration after tissue injury, and = minimizing the=20 risk of cancer. This balance can be examined in mouse models of = inflammatory=20 bowel disease, where, like humans, epithelial damage and chronic tissue = repair=20 occurs.=20

"Ten percent of patients with inflammatory bowel disease go on to get = colorectal cancer," Wong said. "We think that the bone marrow cells aid = in=20 repair of the epithelium, but the cell fusion hybrids that remain are = generally=20 unstable. Fusion may be an underlying molecular explanation of why these = cells=20 might be more susceptible to cancer development."=20

In the PNAS study, Wong and her colleagues transplanted bone marrow = cells=20 from female mice into a male mouse model of intestinal cancer. The = donor-derived=20 cells were readily detected in the intestinal tumors of the male mice.=20

To show that the transplanted donor cells fused with the tumor cells, = the=20 scientists detected proteins or markers from both the female donor and = male=20 recipient cells in tumors. The only way both donor and recipient markers = could=20 be present in a single cell, or colocalized, would be if the two cells = fused.=20

One test to prove cell fusion involved looking for the presence of Y=20 chromosomes, or male-characteristic DNA, within the female donor cells = marked=20 with a green fluorescent protein. About 60 percent of the epithelial = cells were=20 positive for both donor and recipient cell markers. A second test = confirmed=20 colocalization using a confocal microscope, which can scan a single cell = layer=20 of intestinal cells for the presence of both the green fluorescent = protein,=20 indicating female donor cells, and an enzyme from the male recipient = cells=20

Wong said, "Our paper is unique because it's the first example that = cell=20 fusion occurs in the epithelial compartment of a tumor."=20

Other OHSU studies in recent years are giving weight to the fusion = theory. A=20 series of discoveries since 2000 by study co-author Markus Grompe, M.D., = professor of molecular and medical genetics, and pediatrics, OHSU School = of=20 Medicine, and director of OHSU's Oregon Stem Cell Center, showed that=20 blood-forming stem cells derived from bone marrow, called hematopoietic = stem=20 cells, cure liver disease in mice through cell fusion rather than=20 transdifferentiation of the transplanted stem cells.=20

Wong acknowledges fusion is still a new concept. But it's gaining = popularity=20 as a way of explaining the molecular mechanisms that may be at work in=20 regenerating rapidly turning over damaged tissue, or may even be = implicated in=20 disease progression.=20

"The intestinal lining is the protective barrier between your body = and the=20 outside environment. Therefore, it sees all of the offensive = contaminants that=20 you ingest, from the beer you drink to the charbroiled hamburger you = eat, that=20 can induce mutations in the cells. The gut protects itself by rapidly = turning=20 over its epithelial cells. Plus, when there is damage to the surface = lining, it=20 is critical that regeneration and reestablishment of the barrier occurs = rapidly.=20 We think that cell fusion with bone marrow cells is the body's way of=20 jump-starting that regeneration of the epithelium," she said.=20

###

The study was funded by the National Institutes of Health. Other = authors in=20 the OHSU School of Medicine were Adnan Rizvi, M.D., surgical resident in = dermatology; John Swain, research assistant in dermatology; Paige = Davies, Ph.D.,=20 postdoctoral fellow of dermatology; Alexis Bailey, research assistant in = medicine (endocrinology, diabetes and clinical nutrition); Adria Decker, = graduate research assistant in molecular and medical genetics; Holger=20 Willenbring, M.D., former postdoctoral fellow of molecular and medical = genetics;=20 and William Fleming, M.D., Ph.D., associate professor of medicine = (hematology=20 and medical oncology) and cell and developmental biology.=20

To access all OHSU new releases, visit www.ohsu.edu/news/.=20

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