Claudia Fischback-Teschl works at Cornell University in the Department of Biomedical Engineering. She uses engineering approaches to study the micro-environmental control of cancer. One of the PS-OC projects that she directs uses microfabrication approaches to develop culture models to recapitulate some of the micro-environmental conditions that occur in cancer. She also studies the matrix around cancer cells and this is what she spoke about in the conference.
Claudia Fischback-Teschl: So the talk that I gave this morning was specifically related to extracellular matrix remodeling. As I was just explaining, in the context of breast cancer, we have an interest in the role of adipose tissue and are studying how obesity might be changing adipose tissue characteristics (since) in a way, the matrix in adipose tissue is actually very similar to what a tumor would be mediating. And perhaps those changes are playing a role and are responsible for breast cancer patients that are obese having the worst prognosis with regards to the clinical outcome.
Pauline Davies: I think you had the word stiffness in the title, so presumably the adipose tissue gets stiffer, is that the case? Explain how that is related to cancer cell metastases.
Claudia Fischback-Teschl: So, adipose tissue is a very soft tissue and in fact adipose tissue from obese individuals is similarly as soft as the adipose tissue from normal patients. However, there are very localized regions within that adipose tissue that basically result from a lot of extracellular matrix molecules that have been deposited, that are being stretched, being compacted. What researchers have shown in the past is that if there is increased stiffness, that allows tumor cells to basically exert and enhance contractility. And enhanced contractility is important for them to proliferate better, and important for them to migrate better. And both of those characteristics are features of metastasis where individual tumor cells need to be able to dislodge from their original context and migrate into the surrounding tissue; get to blood vessels to be distributed with the blood throughout the body.
Pauline Davies: And you mention that obese patients have a worse prognosis. But it’s also true that obese women have more breast cancer than normal weight women.
Claudia Fischback-Teschl: Correct. It's both an increased risk for incidence of breast cancer, as well as an increased risk for prognosis. When you are specifically asking about incidence, what’s been shown is there is about a 1.2 fold increase in the development of breast cancer in patients with each 5 kg/m² increase in body mass index. So it’s a very significant change in an incidence with becoming obese, basically.
Pauline Davies: What about women who have breast implants? Does this increase stiffness in any sense and are they more at risk?
Claudia Fischback-Teschl: So that's an interesting question. It depends on how you define a breast implant. There are silicone implants that women might have for cosmetic purposes or for reconstructive approaches following a mastectomy. And as far as I understand it, there have been long-term follow-up studies in which people have shown that silicone implants, for example, are not associated with an increased risk of developing breast cancer. However, one of the things to consider is that with every implantation of every artificial material in the body, there is something that's called a foreign body response; which is basically a localized inflammation due to this interface that is being generated. It is almost like a scar tissue and that scar tissue is very similar to the types of tissue remodeling that are happening during tumors. So in that regard it could be that if there're any residual cancer cells that this might be causing an effect, but one of the things that results from our research is that we show that adipose progenitor cells, or adipose stromal cells, which is a specific population of cells that are pursued for reconstructive purposes - primarily in the context of mastectomy - might actually be promoting remodeling of the breast in a way that increases incidence (of breast cancer). In fact there are now clinical studies suggesting that patients who had adipose tissue-based reconstruction potentially might be subject to an increased risk of having recurrence relative to patients who don’t.
Pauline Davies: And where do they get this adipose tissue?
Claudia Fischback-Teschl: So adipose tissue is nice because all of us have typically enough to spare and so a plastic surgeon would go in and take it out from subcutaneous depots, for example, from the belly, and then inject it back into the breast. And it's nice because this is what's called an autograft, so basically the cells of the tissue are coming from the exact same patient so there are no rejection issues and no problems with an immune response.
Pauline Davies: So what implications does your work have for treating people and for treating women who may have had breast cancer?
Claudia Fischback-Teschl: With regard to treatment, I think if I was a woman that had to consider whether or not to get the reconstructive procedure done with adipose tissue, I would like to be certain that the adipose tissue that is being used is thoroughly characterized with regards to its cellular composition and also matrix composition. I don't think we can just bluntly go in, take out tissue and re-implant it somewhere else. We need to understand what this tissue transplant is like. So the specific implications of our work are that it's not just an endocrine effect mediated by an excess number of adiposities, which is what people historically thought is the cause for this negative association. But I think that our results suggest is that it might very much be related to very local mechanics and local phenomena. Also from a broader perspective, a lot of these things that I have just discussed are related to inflammation and one of the considerations is always, could we use, for example, low-dose non-steroidal anti-inflammatory drugs that could help to reduce the local inflammation that is contributing to the extra-cellular matrix remodeling and thus help in basically both in the incidence and prognosis of breast cancer.