Behind the Study: Secretomes in Breast Cancer Cells Induce MSC Actions

Researchers describe their paper published in Oncotarget titled, “Secretomes from metastatic breast cancer cells, enriched for a prognostically unfavorable LCN2 axis, induce anti-inflammatory MSC actions and a tumor-supportive premetastatic lung.” Behind The Study Researchers explain their studies that were published in Oncotarget The Behind the Study series transcribes videos of chosen researchers elaborating on their recent papers published in Oncotarget. Visit the Oncotarget YouTube channel for more insights from outstanding authors. oncotarget journal impact factor Jonathan Kelber Hello. I’m Jonathan Kelber, and I’m a associate professor at Cal State Northridge in the Los Angeles area. I’m currently on my sabbatical leave from there as a Fulbright Cancer Research UK Scholar at the University of Manchester. And today my grad student Francesca and I will be telling you a little bit about our work on our recent publication in Oncotarget titled “Secretomes from Metastatic Breast Cancer Cells, Enriched for a Prognostically Unfavorable LCN2 Axis, Induce Anti-Inflammatory MSC Actions and a Tumor-Supportive Premetastatic Lung.” Oncotarget website Generally speaking, my lab is interested in cancer metastasis and how to overcome that as well as how to overcome therapy resistance in both breast and pancreatic cancers. Francesca Sanchez Hello, my name is Francesca Sanchez, and I am a master student in the Kelber Laboratory at California State University Northridge. Upon the completion of my master’s program, my hope is to matriculate into a doctoral program where I can continue studying cancer progression. Oncotarget Jonathan Kelber So the project that we’ve recently published in Oncotarget had its beginnings back in 2016, actually at the AACR annual conference that was held in New Orleans that year. And it was at the last day in a session entitled “Premetastatic Niches, Exosomes, and Tumor-Secreted Factors” that it occurred to me that most of the work that has been reported in this field has been done or has come to our understanding through the use of immune-deficient animal models. And while that has been for good reasons, since there’s been a number of human tumor cells that have been developed and very well characterized that have specific organotropisms, it also seemed that there was a need for understanding how the premetastatic niche is reprogrammed or primed before tumor cell seeding in the context of models where the immune system is intact. And so as I returned from this meeting and began talking with my current grad student at the time, Ms. Kayla Meade, another first author on the paper, we began trying to devise some plans for how to approach this issue. And we also discovered that a complication in some of the studies in terms of what we were hoping to do was that there are tumor cells being implanted into these models. Now that might sound a little peculiar, since we’re actually trying to study cancer and we do need to know how these tumor cells are behaving in these models, but what we were interested in is understanding how the secreted factors specifically from these tumor cells act to reprogram or prime these premetastatic niches. San Antonio hospitals And so having tumor cells implanted or injected into these models, even potentially immune-competent models, pose a complicating factor, and so we wanted to really hone in on the secretomes. And so Kayla began by taking conditioned media from cells, two cell lines, Py230 and Py8119, a metastatic and a non-metastatic line that were developed by Lesley Ellies out of the MMTV poly middle-T mouse, and injecting those to systemically educate these mice. These were C57 black 6 mice. And then to characterize how the lung and brain tissues were changing histologically as well as looking at some immune and mesenchymal stem cell markers. And, of course, she was interested in how these cells were reprogramming these tissues in comparison to mock conditioned media as a control. And along with an undergraduate in the lab, who’s now moved on to a doctoral program at UC San Diego, Analine Aguayo, she’s also a first author on the paper, they in parallel characterized how these conditioned media samples were affecting either immune cells or mesenchymal stem cells in vitro systems. And, finally, when Francesca came on board last year, she really rounded out the story by developing a method whereby she took out the educated lung tissue from these mice that had received these conditioned media treatments and dissociated the tissue, reconditioned fresh media, and then evaluated how that tissue that had been primed and then subsequently conditioned media would affect tumor cell proliferation or survival ex vivo. I’ll let Francesca tell you a little bit now about what she found interesting in the work.