Prior to working with human cells, I spent several years working with rat models of mammary carcinogenesis and as part of that work, my laboratory developed culture conditions for the long term growth and serial passage of normal rat mammary epithelial cells, and then used that experience to begin developing culture methods for the long term growth and development of cell lines from DMBA-induced rat mammary carcinomas. That experience was valuable, not only because it gave me and my lab a lot of hands on experience working with primary cells from both normal and neoplastic tissues, but more importantly, because the work provided our first insight into the importance of growth factor independence as an in vitro phenotype associated with malignant potential in vivo. Those findings were the springboard for all of our subsequent work on the mechanisms by which the HER2 oncogene regulated expression of transformed phenotypes in rodent breast cancer cells. In addition, the mechanistic connection between growth factor independence and malignant potential is what ultimately led to the development of culture conditions for the growth of human breast cancer cells in vitro, and the development of the SUM breast cancer cell lines.
As I mentioned in a previous blog, I did my post-doctoral fellowship at the Michigan Cancer Foundation and spent five years there before moving on to an Assistant Professor position at the University of Michigan. During the five years I spent at the MCF, I had the opportunity to get to know Dr. Herbert Soule very well and I worked closely with him on some projects. Herb and I shared a New England heritage which helped with our personal relationship, because Herb could be, well, a bit cantankerous. In fact, I was there working right next door to him when he developed the MCF-10A cell line. That is an interesting story that I may share in a separate blog.
Anyway, in 1988 I left the MCF to join the faculty at University of Michigan in Ann Arbor, and in leaving the MCF, Herb was kind enough to give me frozen samples of a number of cells lines he’d been working with including the newly developed MCF-10A and MCF-12. One of the goals that I set for myself in starting my career at Michigan was to make the transition from rodent models of breast cancer to human models. I had become very interested in growth factor independence in breast cancer and I wanted to extend our work into human cell models. But, a major limiting factor for that kind of work was the necessity to work with cells under growth-factor defined culture conditions, as we had done with the rat cells. All of the cell culture methods we had developed for normal and neoplastic rat mammary cells were growth factor supplemented serum-free media, or media with very low serum levels and a series of hormones and growth factors, and we spent several years working out the influence of each of those hormones and growth factors, and their combinations on the proliferative potential of these cell types. Knowing that, it was discouraging to realize that all of the human breast cancer cell lines that had been developed up to that time were developed and cultured under completely undefined conditions, usually consisting of some basal medium and 10% fetal bovine serum. What’s more, the cell lines that everyone in the field worked with had been growing in these poorly defined conditions for many years, including MCF-7 cells. So, it quickly became clear to me that if I wanted to perform the kind of experiments with human breast cancer cells that I did with the rat cells, that I would have to start working with primary cells myself. Fortunately, my department chair at that time was Dr. Allen Lichter, a radiation oncologist who’s clinical interest was in breast cancer. Allen was instrumental in setting up one of the first multi-disciplinary clinics at the U of M Cancer Center, and when I told Allen what my goals were for my research in his department, he invited me to start attending the Monday multidisciplinary tumor board meetings. It was there that I met the surgical oncologists and medical oncologists who were the gate keepers when it came to procuring breast cancer tissue for my experiments. Nothing that I accomplished in the development of cell lines would have been possible without the enthusiastic support of Dr. Lichter, Dr. David August, Dr. Vern Sondak, Dr. Rob Cote, and many others. These docs enthusiastically embraced my research interest and made it possible for me to procure literally hundreds of breast cancer specimens from patients over the next several years. At this point, I need to give a special shout-out to Dr. Barbara Weber for her role in helping me develop the SUM cell line panel. I first got to know Barb when she was doing her Medical Oncology Fellowship at Michigan and was there when she joined the faculty to start her research career. It was Barbara who encouraged me to apply for the first ever Department of Defense breast cancer grant. During the first year of that program, the DOD had a special category for infrastructure grants that were aimed at developing breast cancer biobanks as shared resources. I probably would not have applied for that grant without her encouragement, but I did apply, and received five years of support for the project that ultimately led to the development of the cell line panel, and a bank of hundreds of specimens that were used by researchers at the University of Michigan and elsewhere. To provide an example of that, for anyone who has read the first breast cancer stem cell paper that came from Mike Clarke and Max Wicha’s lab at Michigan, the cells for those experiments came from my biobank, and we were appropriately cited in the Methods section of that paper. That is just one example of the kind of work that we were able to support as a result of the funding for this resource. Given the work that the tissue bank supported and the fact that hundreds of labs have worked with the SUM breast cancer cell lines resulting in over 2000 publications, it is clear that this grant mechanism was incredibly productive and has had a large impact on our field.
As a result of all of this activity, which occurred within the first year or two of me joining the faculty at Michigan, my lab began working with breast cancer specimens that we procured from patients. As I mentioned earlier, I arrived at Michigan with cells that had been given to me by Herb Soule, and all of these cells had an “MCF” designation. So, as we started to isolate and work with cells from the U of M patients, I needed to call them something that would distinguish them from the MCF cells I brought with me. And so, one day, in what was a rather lite moment in the lab, we decided that the cells from these tissues would become Steve’s University of Michigan cells, and hence, the term SUM breast cancer cells was established. I was just a joke at first, but the name stuck, and here we are.
