Latest Short Talks Discusses How Researcher Models Spread of Breast Cancer Using Hydrogels

According to the American Cancer Society, breast cancer is the most common cancer diagnosed in the United States. Approximately one in eight women in the U.S. will be diagnosed with invasive breast cancer, and one in 43 will die from it. Any means of curing it will require better understanding of how it grows and spreads through the body.

This month on Short Talks from the Hill, Younghye Song, an associate professor of biomedical engineering and affiliated researcher with the Arkansas Integrative Metabolic Research Center, discusses her research on breast cancer. (Read the transcript below.)

Song is studying how nerve fibers in breast tumors may act as highways for the spread of cancer.

"Breast tumor innervation is basically a process where you're seeing more nerve fibers or axons infiltrating the primary tumors," Song explains in the interview. "And this whole field of cancer neuroscience is a rapidly emerging field in cancer research. And it is because studies after studies are starting to show that these nerves are not just passive bystanders, but they are active communicators with cancer cells and the surrounding cells that can really fuel disease aggravation."

You can listen to Song's podcast by clicking on the link above or by visiting the home of research and economic development news at the U of A.

And remember, you can now listen to Short Talks programming wherever you get your podcasts.

Thank you for listening!

Podcast Transcript

Hardin Young: Welcome to Short Talks from The Hill, a podcast from the University of Arkansas. I’m Hardin Young, a research and economic impact writer. According to the American Cancer Society, breast cancer is the most common cancer diagnosed in the US. Approximately one in eight women in the U.S. will be diagnosed with invasive breast cancer, and one in 43 will die from it. Any means of curing it will require better understanding of how it grows and how it spreads through the body.

Today’s guest, Younghye Song, is seeking to do just that. She’s an associate professor of biomedical engineering and an affiliated researcher with the Arkansas Integrative Metabolic Research Center. Song uses naturally derived biomaterials as models that can be used to study the progression of diseases, like cancer, and promote tissue regeneration without resorting to animal models. These tissue models help her gain a better understanding of healthy and disease states, with the ultimate aim of developing novel therapeutics to improve patient outcomes. Younghye Song, thanks for coming in.

Younghye Song: Thank you for having me.

HY: So, first of all, this stuff sounds really complicated to me whenever we talk about it. So can you kind of just chart out a little bit how you got into this field? What was your progression from high school, college, PhD, that you get to such complex work?

YS: I wanted to study a major that would honestly get me a job at a pharmaceutical company because my grandfather was suffering from lymphoma back then. And then I learned, hey, you could do biomedical engineering or chemical engineering. And so I did a double major in those in my undergrad. And then when I got to college a lot of people were doing research. I didn’t know what research was until I got to college. And then, my interests sort of shifted during college, so I wanted to gain more experience that would help me get into dental school, honestly. So, yeah, a lot of back and forth. So, I joined the lab that specialized in bone tissue engineering. The lab was run by a professor with a DDS degree, dental surgery. So, I joined his lab, I got introduced to tissue engineering research that way, and I was like, ‘Oh, this is really fun.’

HY: What were they doing in the lab?

YS: They were basically making tissue engineering polymeric scaffolds to treat critical size defects in the bone. So, like, if the bone injury gets too severe, the injury gap goes above a certain size that the bone cannot heal on its own. So you need some surgical intervention. So they were making tissue engineered scaffolds to do that.

HY: And these scaffolds mimic the native bone?

YS: Yeah, in some ways. They are mineralized scaffolds. So they do contain natural mineral components found in the native bones and other synthetic polymers. It does integrate with the body. So I was helping with the histological analysis of those scaffolds. Once they were put in the animals, they let the animals roam around for a few months, and then they take the bones out, and then they process the bones to see the outcomes. I was sort of in that process, initially. And then I got into more of a hydrogel aspects, similar to what I’m doing right now, and studying optimizing hydrogel formation to promote oxygenic differentiation of stem cells. So basically helping stem cells turn into bone forming cells. So, that was also really interesting. And I was like, ‘maybe I want to do more of this.’

So, at the time, grad school seemed like the best way to get into more tissue engineering experience, so I went to grad school. I joined the lab that uses tissue engineering tools but uses that to study cancer. And I thought, that’s just a really fascinating combination. You use tissue engineering not to create grafts or scaffolds that can heal tissues but use it to create mimics of injured or disease tissues and study mechanisms from there. So that’s how I got into the breast cancer space. So it was a little bit of a detour.

In grad school, I was not studying tumor innervation. I was more looking at how these little vesicles secreted by cancer cells can activate resident cells in the breast adipose tissue, and these activated cells, in turn, promote blood vessel formation that would then fuel tumor growth. So I was interested in those vesicles and how they can affect other cells in the tumor microenvironment and so forth. So I was exposed to cancer that way. And then in my postdoc, I joined the lab that uses tissue engineering tools but uses that to study the nervous system or traumatic injuries in the central and peripheral nervous system. So I was kind of like being introduced to both fields.

And then I think around that time, this whole field of cancer nerve crosstalk or cancer neuroscience was emerging, but not a lot was still known. And I thought, ‘Hey, this could be a unique niche I could carve out for myself as I seek to start my independent career.’ So I got into this whole cancer nerve crosstalk or cancer neuroscience field, and then I got to be a part of the AIMRC that you mentioned earlier. And from there, I got to study how metabolic rewiring affects breast tumor innervation. And now that’s one of the major arcs of the research in my lab.

HY: Let’s back up a little bit. Basically, what you’re doing is you’re creating biomaterials. So can you just tell us a little bit about how that works? How are you creating these tissues?

YS: With the biomaterials aspect, my lab primarily uses polymers that are naturally found in the body. So collagen being one of the most abundant biopolymers in the body, we primarily use that. And we can extract collagen from rat tails. So one of the things any new members of my lab get trained on is working with rat tails to isolate collagen from them. So, with those rat tail-derived collagens, you can solubilize them to basically create Jello-like structured materials. In these collagen gels, or hydrogels, you can throw in cells of interest. So, in the case of bone tissue engineering, it would be to stem cells that you can turn into bone forming cells, or in the case of cancer, it could be cancer cells and other cells in the resident tissues called stromal cells, if you want to look at the interactions between the two. And to study neurons, we also throw in some neurons into the gels.”

HY: And where are the cancer cells coming from?

YS: Some cancer cells, we buy them. Others, we get them from a cancer institute in another state that do have these banks of patient-derived cancer cells or normal cells that were transformed in a controlled manner to have cells of the same origin but representing different stages of breast cancer.

HY: And so you introduce these cancer cells into a collagen derived from a rat tail. And does the cancer continue to grow and spread?

YS: Yeah, they do grow and they do secrete things that will recruit other cells to do things for them in a favorable manner.

HY: Just so people can kind of visualize it, how small are these cultures? Are they like microscopic, and you can only see it with a microscope? Or is it a little bit bigger?

YS: The gels you can see with the naked eye. So, one thing we do is we control the thickness of the gels, because we don’t want to introduce any oxygen gradients because that can independently affect cell behavior, and we want to study in a controlled manner. So the thickness is about like a few hundred microns. But the diameter can vary. So gels you can view with the naked eye, and cells, you really can’t.

HY: Alright, so you’ve got these samples. Is breast cancer your primary form of research? Or is that the main focus?

YS: One of the main areas of focus. We also study pancreatic cancer, because their mode of cancer nerve crosstalk is sort of opposite of what we study in breast cancer. So in breast cancer, we study how nerve fibers infiltrate the primary tumors. Whereas in pancreatic cancer, we study how cancer cells invade adjacent nerves to use that as a route to metastasis.

HY: Well, let’s talk about that. So, you’ve mentioned it before, but we didn’t really get into it, so now we can get into it. Breast cancer innervation. What is it? And why do you think it’s sort of, potentially, a key to unlocking the processes of breast cancer?”

YS: So breast tumor innervation is basically a process where you’re seeing more nerve fibers or axons infiltrating the primary tumors. And this whole field of cancer neuroscience is a rapidly emerging field in cancer research. And it is because studies after studies are starting to show that these nerves are not just passive bystanders, but they are active communicators with cancer cells and the surrounding cells that can really fuel disease aggravation. So, studies have shown that these neurons can secrete neurotransmitters and that can really cause cancer cells to proliferate like crazy and then metastasize to other organs. And it can increase pain. And it can also cause immune cells to favor tumor growth. And studies have also shown that stress can really promote metastasis of different types of cancers. It really has to do with the activities of sympathetic neurons that do release neurotransmitters caused by stress. So yeah, studies after studies are starting to show that nerves are real, active, major contributors to cancer aggravation.

HY: I was reading some articles on your work before we had this talk. One of the phrases they use, and I’m sure it came from you, was that they act like a kind of highway for the spread of cancer. But let’s just get it really clear. So, a cancer tumor forms in the breast. And these cancer tumors have a high concentration of nerves. And these nerves appear to be a crucial path of spreading cancer through the body. Is that a fair summation?

YS: I think it is a fair summation. Yeah. I mean, there’s still not a lot known, but yeah, cancer cells have been shown to crawl along these nerve fibers and become more metastatic. So, yeah. HY: Okay. So in your research, what is the intermediate step right now when you’re studying this stuff?

YS: So we’re really trying to understand how this innervation happens. So more of an upstream mechanism of innervation. So, we’re looking at it from a metabolic perspective because cancer cells are known to acquire aberrant, metabolic behaviors. Like addiction to glucose or addiction to glutamine. And so we’re trying to see if those changes into cancer cells can alter their behavior in a way that recruits more nerve fibers into the primary tumors.

HY: So once you kind of figure out that pathway and process, a therapeutic might be a way to starve it of those sugars or to starve it of whatever’s feeding it?

YS: That could be a possibility. But I think we would have to be careful because metabolic targeting alone hasn’t really been that successful. So I think it’ll have to be a combination of metabolic targeting or maybe trying to block what cancer cells secrete that recruits nerve fibers. A combination of both of those maybe.

HY: So I don’t want to put you on the spot, but I know this comes under the category of basic research. So, how far do you think you are from kind of sorting some of this stuff out to the point where you might be the one to say, look, we think this is the process and we think this is how you should attack it. So how far off is something like that?

YS: It’ll be a few more years before we get to that, but, yeah, I don’t know. It’ll be awhile.

HY: I know researchers hate that question because it feels like it’s putting them on the clock. But I do think it’s sort of important that people know that this kind of research takes time. And you have to be willing to work on a horizon of ten years. So I mean, like, you’ve got a research grant, that’s what, it’s a five-year NIH grant that’s specifically targeting this. And I think I saw you got an extension on that?”

YS: This grant allows me to get an extension for two more years.

HY: Alright, so in short, be patient y’all. Younghye Song, thank you for coming in today. It’s a pleasure to have you.

YS: Thank you.

HY: Short Talks from the Hill is available wherever you get your podcasts. For more information and for additional podcasts, visit news.uark.edu/research, the home of science and research news at the University of Arkansas. Music for Short Talks from the Hill was written and performed by local musician, Ben Harris.