Fish Show How Cancer Grows

Rhabdomyosarcoma metastasis in zebrafish

(RxWiki News) Genetic studies in a laboratory favorite, zebrafish, have shown that a pediatric cancer has more than one type of cell involved. Some cancer cells specialize in metastasis while others are content to stay where they are.

This is a new and radical concept in cancer research, which has previously concluded that all cancer cells are sloppy, zombie-like mutants in various stages rather than specialized cells working together to metastasize.

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Contradicting the long-held tumor seeding theory, scientists observed that one type of cell with a mutation in the myf5 gene was able to leave the tumor, penetrate the walls of arteries and establish new colonies. Other cells with the standard myogenin gene stayed where they were, with no migration or metastasis.

Interestingly, the metastasis always followed the same pattern of waiting until the a core of standard permanent myogenin tumor was formed before the traveling metastasis myf5 cells began to leave to start a new colony.

This does correlate with cancer behavior, that development of a tumor generally takes a long time to establish itself before any metastasis occurs.

"Most investigators have thought that tumor-propagating cells – what are sometimes called cancer stem cells – must be the first colonizing cells that travel from the primary tumor to start the process of local invasion and metastasis, but in this model, this is simply not the case," says David Langenau, PhD.

"Instead, the colonizing cells lack the ability to divide and instead prime newly infiltrated regions for the eventual recruitment of slow-moving cancer stem cells. It will be important to test how broadly this phenomenon is found in a diversity of animal and human cancers."

Study coauthor, Myron Ignatius, PhD, expanded on the nature of the research.

"Our direct in-vivo imaging studies are the first to suggest such diverse cellular functions in solid tumors, based on differentiation and the propensity for self-renewal," stated Ignatius.

The implications of several different types of cancer cell within every tumor is something of a revelation, meaning that specialized cells require specialized treatments, which explains the success of toxic general cancer treatments such as older chemotherapies and radiation.

"I think we will find that this kind of division of labor is a common theme in cancer, especially given that the vast majority of cells within a tumor are not tumor-propagating cells. We suspect there will be molecularly defined populations that make niches for tumor-propagating cells, secrete factors to recruit vasculature and create boundaries to suppress immune cell invasion."

Langenau concluded his research by summing up the discovery's importance for cancer treatment.

"Division of labor is a new and emerging concept in cancer research that we hope will lead to new targets for rationally designed therapies. In rhabdomyosarcoma it will be important to target both the tumor-propagating cells and the highly migratory colonizing cells for destruction – a major focus of ongoing studies in our group."

The research was published in the journal Cancer Cell on May 15, 2012.

The study was supported by grants from the National Institute of Health, the Alex's Lemonade Stand Foundation, the Sarcoma Foundation of America, the American Cancer Society and the Harvard Stem Cell Institute. 

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Review Date: 
May 26, 2012
Last Updated:
August 6, 2012