Battling cancer, one cell at a time

October 6, 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: New study reveals improved way to interpret high-throughput biological data

Related Stories

Imaging glucose uptake activity inside single cells

July 17, 2015

Researchers at Columbia University have reported a new approach to visualize glucose uptake activity in single living cells by light microscopy with minimum disturbance. In a recent study published in Angewandte Chemie International ...

New cell division mechanism discovered

July 13, 2015

Canadian and British researchers have discovered that chromosomes play an active role in animal cell division. This occurs at a precise stage - cytokinesis - when the cell splits into two new daughter cells. It was observed ...

Recommended for you

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

(PhysOrg.com) -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...

Quantum Theory May Explain Wishful Thinking

April 14, 2009

(PhysOrg.com) -- Humans don’t always make the most rational decisions. As studies have shown, even when logic and reasoning point in one direction, sometimes we chose the opposite route, motivated by personal bias or simply ...

1 comment

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!

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.