Battling cancer, one cell at a time

Oct 06, 2008

New research suggests that the identification and examination of key cell signaling events required for initiation and progression of cancer might be best accomplished at the single cell level. The research, published by Cell Press in the October issue of the journal Cancer Cell, provides new insight that may lead to better diagnosis and treatment of some complex cancers.

Recent advances in flow cytometry, a technique that allows detailed examination of individual cells, have enabled simultaneous measurement of cell type and signaling pathways. Lead study authors Dr. Garry P. Nolan from the Stanford University School of Medicine and Dr. Mignon L. Loh from the UCSF Children's Hospital and the Helen Diller Family Comprehensive Cancer Center were interested in determining whether examination of cellular signaling abnormalities caused by genetic mutations associated with cancer could provide a precise correlation between aberrant signaling events and disease physiology.

"We had a strong hunch that we could use 'deranged' cellular signaling to track how cancer cell populations behave at diagnosis through therapy, as well as during remission or return of the cancer," explains Dr. Nolan. "By measuring how signaling proteins respond to certain stimuli at diagnosis and which are modified by resistant cancers, we are essentially monitoring key highways that cancers use to drive their own growth. The advantage of diagnosing a patient's cancer at the single cell level provides us an approach for early detection of cancer and yield insights into how cancer cells are responding or adapting to therapy. A byproduct of the single cell technique, when appropriately extended, is that we should eventually be able to predict those pathways cancer cells might be using to circumvent current therapies and more intelligently direct the patient towards alternative treatments."

The researchers focused on juvenile myelomonocytic leukemia (JMML), an aggressive myeloproliferative disorder of young children. JMML is difficult to diagnose and has a complex molecular profile. Although genetic lesions impacting Ras signaling and alterations downstream of the activated GM-CSF receptor (both linked with inappropriate cell growth and survival) have been linked with JMML, there are very few methods for identifying therapeutic agents and assessing efficacy in JMML patients.

The researchers used flow cytometry to profile signaling at the single cell level, including molecules associated with GM-CSF and Ras signaling, for the presence of primary JMML cells with altered signaling behavior that correlated with disease physiology. Cells samples came from JMML patients, healthy individuals and patients with other myeloproliferative disorders, some who had initially been diagnosed with JMML. An unexpected STAT5 signaling signature was seen in most of the JMML patients, suggesting a critical role for JAK-STAT signaling in the biological mechanism of this cancer and suggesting potential targets for future therapies.

"This work successfully used single-cell profiling to follow patients over time and show that disease status in JMML – at diagnosis, remission, relapse and transformation – was indicated by a subset of cells with an abnormal signaling profile," says Dr. Loh. "Revealing cell subpopulations, even rare cells, that are associated with disease opens additional avenues for measuring minimal residual disease, assessing biochemical effects of targeted therapies at the single cell level and understanding drug actions and mechanisms of diseases of heterogeneous origins and manifestations in diverse patient populations."

Source: Cell Press

Explore further: Discovery could lead to new cancer treatment

add to favorites email to friend print save as pdf

Related Stories

Deploying exosomes to win a battle of the sexes

2 hours ago

There are many biological tools that help animals ensure reproductive success. A new study in The Journal of Cell Biology provides further detail into how one such mechanism enables male fruit flies to imp ...

A better understanding of cell to cell communication

Aug 22, 2014

Researchers of the ISREC Institute at the School of Life Sciences, EPFL, have deciphered the mechanism whereby some microRNAs are retained in the cell while others are secreted and delivered to neighboring ...

New tool identifies therapeutic proteins in a 'snap'

Aug 21, 2014

(Phys.org) —In human and bacterial cells, glycosylation – the chemical process of attaching complex sugar molecules to proteins – is as fundamental as it gets, affecting every biological mechanism from cell signaling ...

Why NASA studies the ultraviolet sun

Aug 21, 2014

(Phys.org) —You cannot look at the sun without special filters, and the naked eye cannot perceive certain wavelengths of sunlight. Solar physicists must consequently rely on spacecraft that can observe ...

Histones and the mystery of cell proliferation

Aug 19, 2014

Before cells divide, they create so much genetic material that it must be wound onto spools before the two new cells can split apart. These spools are actually proteins called histones, and they must multiply ...

Recommended for you

Discovery could lead to new cancer treatment

Aug 29, 2014

A team of scientists from the University of Colorado School of Medicine has reported the breakthrough discovery of a process to expand production of stem cells used to treat cancer patients. These findings could have implications ...

Is the HPV vaccine necessary?

Aug 29, 2014

As the school year starts in full swing many parents wonder if their child should receive the HPV vaccine, which is recommended for girls ages 11-26 and boys 11-21. There are a lot of questions and controversy around this ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

E_L_Earnhardt
not rated yet Oct 07, 2008
ELECTRONS, by mass, speed, and spin are the ENERGY deposit within the cell. Excess ENERGY will result in accelerated mitosis, (cancer). Energy may subtracted by cooling, or by electrical withdrawal of electron surplus!