Halting Tumor Cells from Spreading by Blocking 'Hostile Mergers'
About the Researcher
Charles Keller, M.D. Associate Professor
OHSU Knight Cancer Institute
Pediatric Cancer Biology Program
6 Months - 1 year
What your donation will fund:
$19,634 raised:Purchase of live cell tumor environmental chamber for confocal imaging of tumor cell - stem cell fusion
Featured funders of this project include:
We are grateful to the Patrick M. Callahan Memorial Fund for Pediatric Cancer Research, which funded our prior research leading to these new proposed studies.
- Emily Redd
- Donna Cross
- Cheryl Svalina
- Julia Jeschke
- Larry and Julie Nevonen
- Larry and Patricia Nevonen
- Tina Kosha
- ralph hopp
- Adil Lalani
- Mika Pilacinski
- Zona Walcott
- Peter Tripp
- Ty Pettit
- Anne White
- Terri Layden
- Amy Stein
- Elizabeth Radka
- Andrew Labahn
- Teri Marconi
- Sharon and Michael Miller
- Jane Kelly
- Linda Kelly
- Frances Varga
- Sharon and Mike Miller
- Sharon and Mike Miller
- Mike Hollinger
- Teri Marconi
- Arlene Gioia
- Joseph Goedereis
- William Gerber
- Katie Lorenz
- alejandro kitzis
- Don and Claudia Hutchison
- Tracy Borlaug
- Argia Riggs
- Jessica Owens
- Stacey Wendt
- Kristen Lindquist
- Kyle Bell
- Lee Ritter
- Lee Ritter
- Lee Ritter
- Jesse Larson
- Lee Ritter
- Kara Larson
[ See the Consano story by Cathy Marshall (KGW, NBC Portland Channel 8) at http://www.kgw.com/home/breast-cancer-mom-225379922.html]
[ See a video introduction to our project at http://www.youtube.com/watch?v=Oq02oni1k5c ]
Childhood muscle cancer is extremely difficult to cure when the cancer cells have spread throughout the body. Our preliminary data suggest that this cancer might actually use our very own stem cells and normal cell-to-cell communication system to metastasize. We believe tumor cells 'talk' to muscle stem cells and convince them to secrete growth factors that enable tumor cells to spread to new sites in the body. In fact, it also appears that tumor cells fuse to muscle stem cells - more than just cell-to-cell talk, and a rather unexpected 'hostile merger'. We have identified a specific receptor that appears to be responsible for this effect. With a blocking antibody to the receptor we can already stop the spreading of tumors to lymph nodes or to the lungs in mouse experiments. While the same kind of blocking antibodies have had successful safety testing in asthma studies by pharmaceutical companies, we have one last critical series of experiments to conduct before partnering to apply our results to the clinic: we must test whether fusion of tumor cells to normal stem cells is the key event, or whether metastasis results when tumor cells and normal stem cells simply cross-talk without merging/fusing. Either possibility exists, but would change the way the intervention is taken to clinical trials. We are seeking to raise $19,634 for the key experiments (1) to observe the time course of tumor cells fusing with normal stem cells, and (2) to test whether fused cells are more or less capable of establishing tumors than mixed but unfused cells. This experiment can be completed within 6 months of raising project funds, and the results will be not only sent for publication, but also shared with (i) the Children’s Oncology Group clinical trial committee for rhabdomyosarcoma and (ii) a major pharmaceutical company with the appropriate therapeutic antibody that might be used in a clinical trial for children with rhabdomyosarcoma.
Why is this important?
We believe our finding of how tumor cells actually use our own stem cells to metastasize is a largely new paradigm that may be relevant to cancers of adults and children alike. Thus, our study begins with the solid tumor of muscle, rhabdomyosarcoma, but may spark similar studies (and similar kinds of treatment) for other tumors if our hypothesis is correct.
Who will benefit from the results of this project?
Charles Keller, M.D. Associate Professor
It is the personal connection that drives much of what we do in our laboratory. I was profoundly influenced early in my training by a young woman with alveolar rhabdomyosarcoma. A vibrant young person with all of life ahead of her. I attended her engagement party, but not long later her disease recurred and she, as others before her, succumbed to the disease. Our research team feels accountable to these families to deliver tangible results --- credible and exciting research findings that also bring treatments to the clinic. To remind ourselves of this mission, our laboratory makes patients and families an active part of our research team.
One of the activities our laboratory is proud to have hosted is a Pediatric Cancer Nanocourse for parents of children affected by childhood cancer. Our ongoing partnership with these parents has led not only to the Patient Wall, but also co-authored manuscripts on initiatives so important as pediatric cancer autopsies for research. Parent partners have also been instrumental in the "Open Science Forum" concept for weekly blog reporting of our international effort to find a 2-drug targeted treatment to move to clinical trials for the uniformly fatal brain stem glioma of childhood.
The most exciting aspect of our research program is the multi-disciplinary collaboration… molecular biologists, stem cell scientists, biochemists, clinicians and electrical engineers. This project is made possible through these specific types of collaborations.
Education & Training
|2001||University of Utah||Fellowship||Pediatric Hematology-Oncology|
|1998||Baylor College of Medicine||Residency||Pediatrics|
|1995||Baylor College of Medicine||M.D.||Medicine|
|1990||Tulane University||B.S.E.||Biomedical Engineering|
hi, All. this is an example of the data from the attachment (https://vimeo.com/84554859). Shown is differentiating satellite cells (muscle stem cells) on their way to becoming myoblasts and multi-nucleated myotubes. We sure do appreciate this instrument - it has been, and continues to be, so valuable to our research! Charles
We are grateful to everyone who made this possible... the attachment for the microscope arrived & was installed late last week! Megan is already generating time lapse data, and we hope to share a sample with you in the coming weeks. Thank you again for supporting this rhabdomyosarcoma research!
3 Days left!
Yesterday we presented our study results at the Children's Oncology Group meeting to an audience of pediatric oncologists, scientists, pathologists and other medical care providers who specialize in rhabdomyosarcoma - the work was very well received ("you're really onto something" was the essence of one prominent expert's comment!) And of course there came a question about approaching the issue of fusion by a time lapse approach... which is indeed! the goal of this Crowdfunding Project!
so... we're down to the home stretch, and we are so grateful for all of your support for our project! Together, we might really bring this scientific observation towards clinical (clinical trial) application!
We would be so grateful if you can all share out project for this last hoorah!
We are looking forward to keeping you all updated going forward, too.
ps. thank you, Donna, for your recent contribution!
See the Consano story by Cathy Marshall (KGW, NBC Portland Channel 8) at http://www.kgw.com/home/breast-cancer-mom-225379922.htm !
our thanks to advocates (home stretch)
Our thanks to Cynthia and other advocates that are helping get the word out on the last stretch of the project. Now more than ever we need this special instrument to do our studies. It's all part of trying to convince ourselves of the mechanism, and the pharma company of the worthiness, of taking this approach for children with rhabdomyosarcoma.
The paper describing our initial results is now published online by the journal StemCells, http://onlinelibrary.wiley.com/doi/10.1002/stem.1491/abstract. Megan has an exciting next-steps, multi-week project underway.
We are half way to our crowdfunding goal, and are rather excited about how (with a modest amount of additional data) we migth take a shelved treatment for asthma and turn it into a maintenance therapy for rhabdomyosarcoma that prevents tumors from being established at metastatic sites.
Thank you, Cheryl, for your contributions to our project this week!
update (final video take!)
We have a full video description of our project now available at http://www.youtube.com/watch?v=Oq02oni1k5c . We are also grateful for the very generous contributions this week of Larry & Patricia, Larry & Julie and Tina. We really appreciate your partnership that makes this rhabdomyosarcoma research possible.
video update (take 1!)
For an introduction of our team and this community-lab partnership project, please see our video at http://kellerlabblog.blogspot.com/2013/07/new-update-on-crowdfunding-project.html . Again, thank you for everyone making this possible (and those who will become new partners).
update (great news)
Congratulations to lab alumnist, Guangheng (GH), whose related paper of pilot studies on rhabdomyosarcoma - satellite cell (muscle stem cell) interactions has just been accepted for publication in the journal StemCells. Co-authors include lab members Ken and Megan, lab alumnist Ken, and long time collaborator Brian Rubin at the Cleveland Clinic. Our sincere thanks to Matthew for his technical assistance on these studies.
For this project, GH was supported by a fellowship from the Scott Carter Foundation and study reagents were made possible by support of the Patrick M. Callahan Memorial Fund.
Stay tuned for when the manuscript is available online.
ps. Adil and Ralph, thank you for your contributions this past week. We really appreciate it.
We've just submitted preliminary studies to a scientific journal for peer review. Meanwhile, we really appreciate the support of Amy, Terri, Anne, Ty, Peter, Zona, Mika and our anonymous donors for becoming partners in research. Last week we did some filming in the lab to introduce our team and discuss the project, but this week we'd like to share the excerpt of Megan describing her project at http://kellerlabblog.blogspot.com/2013/07/megan-discusses-community-partnering.html.
Thank you again for your support. You're making this research possible!
Megan continues to be deep into the experiments, isolating muscle stem cells and generating tumor cells for the mixing and fusion experiments. We are grateful to Elizabeth for her support of the project... Now in the final 3 weeks !
Isolated muscle cells in green
We so much appreciate the community partnership on this project. We hope it is a paradigm for open communication of research projects with the community. If it is a success, it will be because of the great support from you.
from Megan, a technical update: Next week we will be using Tamoxifen therapy to induce Cre recombination in Pax7 expressing cells of membrane tomato mice, causing these cells to express membrane GFP rather than the ubiquitous RFP. Muscle harvesting and tissue culturing will be preformed and flow cytometry will be used to sort the cultured cells into a GFP positive and GFP negative population. The result will be a pure population of satellite cells (those expressing Pax7/GFP) which will be co-cultured with alvolar rhabdomyosarcoma cells expressing cytoplasmic RFP. After 36 hours the cells will be flow sorted again, this time for the presence of multinucleated cells with green membranes and red cytoplasm, indicating the fusion of these two cell lines.
from the entire lab team: Our sincere thanks to Teri and Andrew for your contributions to this community - research team partnership!
We are following a key set of tumors developing for Megan's proof-of-concept fusion studies. Once a little larger, we can harvest the tumors for visualizing the glowing, fused cells. We are grateful to Frances, Sharon & Mike M. and Mike H. for their contributions to the funding of this project. Incidentally, if any of our community partners wish to tour the lab, we would be happy to have you visit.
The project is in watchful waiting this week. No progress to report.
In parallel to Megan's experiments, Jinu just started experiments that rule in/rule out major or minor contributions of the immune system to the process we see. We've previously ruled this out in a way, but Jinu is going the extra mile with a multi-week tour-de-force experiment.
Megan's experiment is ongoing, and she is repeating some aspects from last week this week. There is some signal, but we'll need to be patient and see what the experiment shows... the hardest part about a life in research!
We really appreciate the generous contributions of our community partners, Teri, Arlene, Joseph, Bill (hi, Bill!), Katie, Alejandro, Don, Claudia and Tracy.
Megan in our lab is doing a great job creating new tumor cell - muscle stem cell fusion events that we hope will go from a red glow to a green glow when the fusion occurs. It will take 2-3 weeks to know if we'll have the proper cells to study. Of course, the instrument will be key to detecting and measuring this event. Still, we'll be ready if the project meets its goal.
We are grateful to Argia, Jessica, Stacey, Kristen, Kyle, Lee, Jesse, Kara and the anonymous donor for jumpstarting this Consano project with the community.