One Small Step For Open Science, One Giant Leap For Metastasis Research
By Deborah Borfitz
August 3, 2020 | In a first-of-its-kind collaboration, researchers from 19 academically affiliated international laboratories have agreed to share their cell line models specific to brain metastasis with pretty much anyone who asks for them—provided, in most instances, that they not be used for commercial purposes. The menu of options is now publicly available at a central website location, together with basic information such as how to raise the cells in a dish, when to separate them so they don’t overgrow and die, and how they behave in a mouse, according to Amanda E.D. Van Swearingen, Ph.D., senior research associate at the Duke Center for Brain and Spine Metastasis.
The Brain Metastasis Cell Lines Panel (BrMPanel) is an effort coordinated by the Brain Metastasis Group, led by Manuel Valiente, DVM, Ph.D., at the Spanish National Cancer Research Centre, and is believed to represent the majority of such models in existence, says Van Swearingen. BrMPanel is an “invaluable resource,” knocking years off the time, as well as the associated costs, it would otherwise take scientists to build and optimize similar models on their own from scratch. “Some of the models don’t exist anywhere else.”
A full description of BrMPanel, and the unmet need motivating its creation, was detailed in a recent article in Cancer Research (DOI: 10.1158/0008-5472.CAN-20-0291). Many otherwise effective therapies don’t get into the brain, notes Van Swearingen. “The brain ends up being a sanctuary of sorts where a secondary tumor can grow even if the disease below the neck is controlled.”
Between 10% and 30% of all cancer patients develop brain metastases and its rate of occurrence is increasing across most primary cancers, Van Swearingen says, but currently breast, lung, and melanoma are the “big three.” Two of the main challenges are understanding why some tumor cells manage to overcome the strong defensive barriers of the brain against metastases and to develop therapies against this phenomenon.
Legal stipulations are specific to each lab contributing to BrMPanel, says Van Swearingen, in part because policies differ institution to institution and intellectual property laws aren’t the same the world over. Typically, the requesting institutions can’t use the cell line models for any sort of commercial development. But pharmaceutical companies might at minimum want to use the platform to identify academic collaborators for their oncology R&D programs.
Researchers wanting to procure models from the BrMPanel simply need to reach out to the indicated contact for each model at the website and in the Cancer Research paper. Recipient researchers would have only to cover the cost of shipping the frozen cells to their desired destination, an “incidental” expense with the possible exception of those needing to make a transoceanic journey, she says. Cell lines are often freely distributed among academic researchers since their efforts are publicly funded by the National Institutes of Health or its equivalent in other countries. But BrMPanel may well be the first time that knowledge sharing has happened on such a broad scale in one easily accessible place.
Many of the models in BrMPanel have been specially tested and developed in the lab to be brain metastatic, which is not the type of cell lines available from commercial suppliers, says Van Swearingen. These cells lines may have originated with cells that were purchased or came out of a mouse tumor model that didn’t spread to the brain with any regularity. But they were coaxed through multiple rounds of the selection process, over as many as three to five years, to metastasize there “to the point where some of these models go fairly exclusively to the brain.”
One of the scientifically intriguing questions is what biological changes occur in brain metastasis cells that make them different from cells native to the primary cancer site, she says.
At present, the BrMPanel comprises 60 cell lines (animal and human) contributed by many of the leading labs in the field, Van Swearingen says. Cell line models of primary breast, lung, and melanoma cancers are represented. Breast cancer models are most numerous, partially as a reflection of where research efforts are focused.
Far fewer models are available for lung cancer, particularly small cell lung cancer and those with mutations in a gene known as ALK, she says. Ditto “spontaneous” models where cancer traveled to the brain on its own from a primary tumor, which are especially difficult to develop.
The platform is expected to grow as new models are developed and contributed, Van Swearingen says. New additions of all model types are always welcome and the process is fairly straightforward—email Valiente and answer a short list of questions about the cell line type, culture conditions, animal modeling details, and care and feeding of the cells.
Each of the cell lines comes with a “user manual” of sorts, and the BrMPanel website serves as the central repository for that contributed information, Van Swearingen says. “These kinds of things seem really mundane but are critical to making sure not only that you culture cells in the correct manner but in a way consistent with how other researchers used them so your results and theirs can be directly compared.”
Valiente reports that within days of the Cancer Research paper’s publication he was being contacted by researchers around the world wanting to obtain some of the cell lines and proposing new ways the platform might be used. The assumption is that BrMPanel will be utilized for three primary activities: to investigate the biology of brain metastasis cells across multiple models, to test new drugs and novel therapeutic strategies, and to examine hypotheses that emerge from clinical trials or hunt down a response marker for treatment.
Indeed, models in BrMPanel have already proven their translational potential. Van Swearingen highlights that “several published studies with BrMPanel models provided preclinical proof-of-concept evidence for clinical trials in brain metastasis treatment,” which are outlined in the Cancer Research paper.
Collaborators for the BrMPanel are encouraging researchers focused on metastasis to other organs, including the bones, liver, and lungs, to undertake a similar effort. “Cancer can spread to anywhere in the body and it is becoming more and more appreciated that each organ has its own environment which can drive different biology,” says Van Swearingen.
Based on the experience in building BrMPanel, time and effort would be the biggest investment beyond creating and hosting of a website, which is “basically just one gigantic Excel spreadsheet,” she says. BrMPanel does not house any of the analysis conducted on the cell lines, which can be extensive. With the inclusion of data from sequencing, staining and panels of diagnostics run on the cell lines, cost and infrastructure would be a larger consideration, she adds.
Editor’s note: Van Swearingen will be giving an oral presentation on BrMPanel and the Cancer Research paper at the SNO Brain Mets virtual conference on Aug. 14.