A study from Massachusetts General Hospital (MGH) researchers suggests that specific populations of tumor cells have different roles in the process by which tumors make new copies of themselves and grow.
In their report in the May 15 issue of Cancer Cell, researchers identify a tumor-propagating cell required for the growth of a pediatric muscle tumor in a zebrafish model and also show that another, more-differentiated tumor cell must first travel to sites of new tumor growth to prepare an environment that supports metastatic growth.
"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, of the MGH Department of Pathology and Center for Cancer Research, who led the study.
"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."
Langenau's team has long been using zebrafish to study rhabdomyosarcoma (RMS), an aggressive pediatric cancer. In embryonic zebrafish, RMS can develop within 10 days, and since the tiny fish are transparent at that stage, fluorescent markers attached to particular cellular proteins can easily be imaged. The current study used these properties to monitor how specific populations of tumor cells develop and their role in initiating new tumor growth.
Previous research from the MGH team had discovered that RMS cells expressing marker proteins also seen on muscle progenitor cells had significantly more tumor-propagating potential than did other tumor cells. Fluorescently labeling proteins associated with different stages of cellular differentiation revealed distinct populations of RMS cells in the zebrafish model. Cells expressing the progenitor cell marker myf5, were labeled green, and those expressing myogenin, a marker of mature muscle cells, were labeled red.
In a series of experiments, the research team confirmed that myf5-expressing RMS cells had powerful tumor-propagating potential, but the ability to visualize how tumor cells move in living fish produced a surprising observation. While myf5-expressing cells largely remained within the primary tumor itself, myogenin-expressing RMS cells easily moved out from the tumor, entering the vascular system and passing through usually impenetrable layers of collagen. Only after the more-differentiated but non-proliferative myogenin-expressing cells had colonized an area did the myf5-expressing tumor-propagating cells appear and start the growth a new tumor. Imaging the labeled tumor cells also revealed that different cellular populations tended to cluster in different areas of later-stage tumors.
"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," says Myron Ignatius, PhD, of MGH Pathology and Center for Cancer Research, the study's first author. "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 adds, "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 distruction – a major focus of ongoing studies in our group." Langenau is an assistant professor of Genetics at Harvard Medical School and a principal faculty mmber at the Harvard Stem Cell Institute.
Additional co-authors author of the Cancer Cell article are Eleanor Chen, Adam Fuller, Ines Tenente Rayn Clagg, Sali Liu, Jessica Blackburn, MGH Pathology and Center for Cancer Research; Andrew Rosenberg, and Petur Neilsen, MGH Pathology; Natalie Elpek and Thorsten Mempel, MGH Center for Immunology and Inflammatory Diseases; and Corinne Linardic, Duke University Medical Center. 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.
Massachusetts General Hospital (www.massgeneral.org), founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $750 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.
Sue McGreevey | EurekAlert!
Further reports about: > Cancer > Cancer Cell > Gates Foundation > Medical Wellness > Stem Cell Institute > Stem cell innovation > cancer stem cells > cell death > cellular function > cellular protein > immune cell > neurodegenerative disorder > primary tumor > stem cells > tumor cells > tumor growth
Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland
Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy