Navigation Links
Protein in embryonic stem cells control malignant tumor cells
Date:3/3/2008

CHICAGO --- 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 researcher Mary J. C. Hendrix, M.D., 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 Childrens 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 hECs 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.


'/>"/>

Contact: Marla Paul
marla-Paul@northwestern.edu
312-503-8928
Northwestern University
Source:Eurekalert

Related medicine news :

1. Novel mechanism found that may boost impaired function of leukemia protein
2. Cancer-related protein may play key role in Alzheimers disease
3. Atypical protein kinase C stabilizes SRC-3 levels in breast cancer cells
4. Blocking protein kills prostate cancer cells, inhibits tumor growth, Jefferson scientists find
5. Urine protein may be present before hypertension diagnosis in at-risk adolescents
6. VBI, Mayo Clinic investigate link between fungal proteins, innate immunity and asthma
7. Researchers identify and shut down protein that fuels ovarian cancer
8. Out-of-whack protein may boost Parkinsons
9. Scientists identify proteins that help bacteria put up a fight
10. Protein shines light on cancer response
11. 3 newly discovered ERK pathway proteins related to CagA induced disease
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/28/2017)... ... April 28, 2017 , ... Ushio America ... lamps offer an instant energy-saving solution for F32T8 fluorescent lamps on most instant-start ... ballasts. These 50,000 hour rated lamps utilize the existing electronic ballast, saving labor ...
(Date:4/28/2017)... Manhattan New york (PRWEB) , ... April 28, ... ... is pleased to announce that Aditya Patel M.D. has joined the revolutionary endoscopic ... fellowship training and board certification in Interventional Pain Medicine. The patented, revolutionary eDiscSculpt ...
(Date:4/28/2017)... Edinburg, Texas (PRWEB) , ... April 28, 2017 , ... ... a plaque in recently to the labor and delivery team at Women’s Hospital at ... generous mothers who give birth at the hospital and decide to donate. , ...
(Date:4/28/2017)... ... April 28, 2017 , ... Early detection and elimination ... safety and minimize the cost of development. In this webinar, sponsored by Molecular ... lines and for cardiac toxicity using induced pluripotent stem cells (iPSCs). , In ...
(Date:4/28/2017)... ... 28, 2017 , ... Bill Howe started his sewer and drain company in ... Howe joined the team, the Bill Howe brand was born and they began cultivating ... giving back to the San Diego community in which they worked, lived and were ...
Breaking Medicine News(10 mins):
(Date:4/20/2017)... Texas , April 20, 2017  Vivify Health, ... mobile devices, has been awarded a very significant patent ... via EMRs to continual care via digital health.  This ... key intellectual property and further secures Vivify,s position as ... launched in 2009, was the first company to apply ...
(Date:4/20/2017)... WOONSOCKET, R.I. , April 20, 2017 /PRNewswire/ ... (NYSE: CVS), today unveiled a new store design ... new assortment of healthier food, health-focused products and ... the store to help customers discover new offerings. ... represent the next evolution of the customer experience ...
(Date:4/20/2017)... LUND, Sweden , April 20, 2017 /PRNewswire/ ... OTCQX: NEVPF) ("NeuroVive") today announced positive preclinical ... company,s preclinical compound for non-alcoholic steatohepatitis (NASH), ... NV556 has previously ... STAM™ NASH model. Today, NeuroVive,s scientists present ...
Breaking Medicine Technology: