Navigation Links
Protein in Human Embryonic Stem Cells Controls Malignant Tumor Cells
Date:3/5/2008

CHICAGO, March 5 /PRNewswire-USNewswire/ -- A protein that governs development of human embryonic stem cells (hESCs) also inhibits the growth and spread of malignant melanoma, the deadliest skin cancer, Northwestern University researchers have discovered. Metastatic melanoma, which develops from the transformation of skin pigment cells or melanocytes, has a death rate of more than 80 percent and a median survival of less than 7.5 months.

The Northwestern scientists, led by noted researcher Dr. Mary J. C. Hendrix, additionally found that the protein, called Lefty, prevents aggressive breast cancer cells from metastasizing. Death from metastatic breast cancer exceeded 40,000 in 2007, with over 180,000 new cases diagnosed in the United States.

Importantly, Lefty is secreted only in hESCs, and not in any other stem cell type tested - including stem cells isolated from amniotic fluid, cord blood or adult bone marrow - or placental cells.

Results of the study, described in an article in the March 3rd online version of The Proceedings of the National Academy of Sciences, build on an elegant body of research by the Hendrix lab to identify the genes and cellular pathways involved in cancer metastasis.

Dr. Hendrix is president and scientific director of the Children's Memorial Research Center and professor in The Robert H. Lurie Comprehensive Cancer Center of Northwestern University and at the Feinberg School of Medicine. Lynne-Marie Postovit, who was first author on the study and a post-doctoral trainee in the Hendrix lab, is currently an assistant professor at the University of Western Ontario, Canada.

Embryonic stem cells are pluripotent, meaning they can become any of 200-plus cell types in the adult body, depending on the signals they receive from their microenvironment (surrounding cells, tissues and vasculature). During cancer progression, malignant cells also receive and release signals from their microenvironment, cues that promote tumor growth and metastasis.

Groundbreaking work by Hendrix and colleagues is elucidating how, by becoming more like unspecialized stem cells, aggressive melanoma cells gain enhanced abilities to migrate, invade and metastasize while remaining virtually undetected by the immune system.

Hendrix and co-researchers previously demonstrated that a three-dimensional matrix conditioned by hESCs induced metastatic melanoma cells to revert to a normal, skin cell-like type with the ability to form colonies in the manner of hESCs (Postovit and Seftor et al, Stem Cells 24:501-505, 2006).

"This observation allowed us to appreciate the powerful influence of the hESC microenvironment on the reprogramming of metastatic melanoma cells," Hendrix said.

In subsequent experiments, Hendrix, Postovit and co-researchers found that aggressive melanoma and breast cancer produce a "morphogenic" protein called Nodal, which is essential for human embryonic stem cell pluripotency (Topczewska et al, Nature Medicine 12:925-932, 2006). Other researchers have found that Nodal also is present in testicular cancer.

"Thus, Nodal may serve as a prognostic marker of aggressive behaviors in human cancers," Hendrix said.

As described in the PNAS study, the Lefty protein inhibits production of Nodal and therefore plays a major role in embryonic cell differentiation and development - under normal circumstances.

Hendrix and colleagues discovered that metastatic tumor cells do not express Lefty, allowing them to overproduce Nodal in an unregulated manner.

However, when the group exposed metastatic tumor cells to the microenvironment of hESCs containing Lefty, they witnessed dramatically reduced Nodal expression (production) in these cancer cells together with decreased tumor cell growth and invasiveness and an increase in apoptosis, or programmed cell suicide.

Although exposure to a hESC microenvironment inhibited Nodal expression and tumor growth in both metastatic melanoma and breast cancer cells, the breast cancer cells underwent more complex reprogramming. Melanoma cells responded to the hESC-derived factors within three days, but breast cancer cells required two additional days to achieve the most significant reduction in Nodal.

This discrepancy is likely due to differences in signaling mechanisms between the two cell types. Yet, despite the inherent differences between melanoma cells and breast cancer cells, these divergent tumor types both underwent cell suicide following exposure to the hESC microenvironment.

"The remarkable similarity of the responses of the two tumor types is likely attributable to the commonality of plasticity (for example, the aberrant and unregulated expression of Nodal) that indiscriminately unifies highly aggressive cancer cells, regardless of their tissue of origin," Hendrix said.

"Further, the tumor suppressive effects of the hESC microenvironment, by neutralizing the expression of Nodal in aggressive tumor cells, provide previously unexplored novel therapeutic modalities for cancer treatment," Hendrix said.

However, while findings from the study suggest that hESC-derived Lefty may have potential to prevent metastasis, it is not the only tumor suppressive factor within the embryonic microenvironment.

Observations from the study highlight the potential utility of isolating factors within the hESC microenvironment responsible for influencing tumor cell fate and reversing the cancerous properties of metastatic tumor cells, such as melanoma and breast cancer.

Additional contributing authors on the study include N. Margaryan; E. Seftor; D. Kirschmann; D. Abbott; W. Wheaton; A. Lipavsky; and R. Seftor.

This study was supported by grants from the Illinois Regenerative Medicine Institute; the National Institutes of Health (CA50702 and CA121205); the Charlotte Geyer Foundation (to Dr. Hendrix); and a Canadian Institutes of Health Research Postdoctoral Fellowship (to Dr. Postovit).

.


'/>"/>
SOURCE Northwestern University
Copyright©2008 PR Newswire.
All rights reserved

Related medicine news :

1. Sticky blood protein yields clues to autism
2. Penn scientists find a protein that inhibits Ebola from reaching out to infect neighboring cells
3. Embryonic Stem Cell Protein Inhibits Melanoma
4. Protein in embryonic stem cells control malignant tumor cells
5. Novel mechanism found that may boost impaired function of leukemia protein
6. Cancer-related protein may play key role in Alzheimers disease
7. Atypical protein kinase C stabilizes SRC-3 levels in breast cancer cells
8. Blocking protein kills prostate cancer cells, inhibits tumor growth, Jefferson scientists find
9. Urine protein may be present before hypertension diagnosis in at-risk adolescents
10. VBI, Mayo Clinic investigate link between fungal proteins, innate immunity and asthma
11. Researchers identify and shut down protein that fuels ovarian cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... ... June 27, 2016 , ... Quality metrics are proliferating in cancer ... they remain in the eye of the beholder, according to experts who offered insights ... American Journal of Managed Care. For the full issue, click here . , ...
(Date:6/26/2016)... Lake Orion, Clarkston, Michigan (PRWEB) , ... June ... ... direction with respect to fertility once they have been diagnosed with endometriosis. These ... tolerable intercourse but they also require a comprehensive approach that can help for ...
(Date:6/25/2016)... Lewisville, TX (PRWEB) , ... June 25, 2016 , ... ... in the United States, named Dr. Sesan Ogunleye, as the Medical Director of its ... be the facility Medical Director of our new Mesquite location,” said Dr. James M. ...
(Date:6/24/2016)... ... June 24, 2016 , ... A recent article published June ... with. The article goes on to state that individuals are now more comfortable seeking ... common operations such as calf and cheek reduction. The Los Angeles area medical group, ...
(Date:6/24/2016)... ... ... Global law firm Greenberg Traurig, P.A. announced that 20 Florida attorneys are recognized ... this recognition are considered among the top 2 percent of lawyers practicing within the ... this year’s Legal Elite Hall of Fame: Miami Shareholders Mark D. Bloom, Burt ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... 2016  Collagen Matrix, Inc., ("Collagen Matrix") the ... of collagen and mineral based medical devices for ... Bill Messer has joined the company as ... the growing portfolio of oral surgery, neurosurgery, orthopaedic ... joins the Collagen Matrix executive team as an ...
(Date:6/24/2016)... CAMBRIDGE, Mass. , June 24, 2016 /PRNewswire/ ... the Spaulding Rehabilitation Network,s Dean Center for ... of Physical Medicine and Rehabilitation, MIT Hacking Medicine, ... Center for Innovation, today announced the five finalists ... Hackathon for Lyme disease.  More than 100 scientists, ...
(Date:6/24/2016)... 24, 2016 Research and ... "Structural Electronics 2015-2025: Applications, Technologies, Forecasts" report ... In-Mold Electronics, Smart Skin, Structural Health Monitoring, ... Structural electronics involves electronic and/or electrical components ... replacing dumb structures such as vehicle bodies or ...
Breaking Medicine Technology: