Stage 4 Studies: ChE Senior Researches Metastatic Breast Cancer Cells
Though treatment for breast cancer patients proves successful in most cases, a large
percentage of patients relapse with metastatic breast cancer, meaning the cancer has
spread to other parts of the body.
Accounting for 90 percent of cancer-related deaths, metastases, also known as stage 4 cancer, are harder to treat since the cancer is often resistant to localized therapies such as surgery or radiotherapy. For the past two years, 海角社区 Chemical Engineering (ChE) senior Grant Landwehr has studied metastatic breast cancer cells in order to help develop new treatment strategies and therapies against secondary metastasis.
鈥淏asically, what we鈥檙e trying to do is better understand cancer at a fundamental level,鈥� said Landwehr, a native of Covington, La. 鈥淲e鈥檙e not looking at if we need to treat metastatic cancer differently, but the why. If we know why they鈥檙e behaving differently, then we can one day prevent them from being more metastatic.鈥�
In order to do this, Landwehr has been working alongside 海角社区 ChE Professor Adam Melvin to discover how fluid shear stress forces affect metastatic cancer cells by looking at how the cells behave biophysically. In metastasis, a tumor sheds a small number of cancerous cells called circulating tumor cells (CTCs) that spread throughout the body to form secondary metastasis. As the CTCs move throughout the circulatory system, they experience physiological forces not present in the initial tumor environment, namely, fluid shear stress (FSS).
鈥淓vidence suggests that CTCs respond to FSS by adopting a more aggressive phenotype,鈥� Landwehr said.
Landwehr鈥檚 work in the lab entailed designing a microfluidic device to isolate and study the response of single breast cancer cells to conditions experienced in the circulatory system during metastasis. He studied the differences in two model breast cancer cell lines, including a triple negative cell line and an estrogen receptor positive cell line, that respond to treatment differently. Landwehr鈥檚 project differs from previous studies in that they utilize a microfluidic device to study how FSS alters single cells.
鈥淏oth cell lines exhibited greater deformability due to increasing duration and magnitudes of FSS,鈥� Landwehr said.
In a nutshell, the greater the FSS, the more aggressive the cancer cells are predicted to become on their journey to creating a metastatic tumor. Landwehr鈥檚 research also found that certain cells rapidly deformed but reached a threshold value after five minutes of FSS, while other cells deformed at a slower rate but with a larger threshold of deformation.
鈥淯ltimately, this behavioral diversity suggests the presence of distinct cell subpopulations with different phenotypes,鈥� he said. 鈥淭he bottleneck effect observed in these cell populations suggests FSS alters the phenotype of cells in such a way that cells begin to act similar to other cells under more intense magnitudes and durations of FSS. These findings would not be possible without the use of a microfluidic device.鈥�
鈥淧erforming single cell studies is of increasing importance,鈥� Melvin said, 鈥渁s several reports have demonstrated a significant heterogeneity across a population of cancer cells.鈥�
This heterogeneity oftentimes results in drug resistance and relapse because primary treatment options fail to eliminate the entire population of cells.
鈥淪tudying single cells is just like grading individual students in a classroom,鈥� he said. 鈥淢ost students wouldn鈥檛 be happy getting the class average; however, that is a common-approach use to characterizing cancer cells.鈥�
Metastatic breast cancer cells frequently differ from the preceding primary breast cancer cells in that they often develop resistance to several lines of previous treatment and have acquired several properties that permit them to metastasize to distant sites. Metastases can be treated, sometimes for many years, but it cannot be cured.
With Landwehr鈥檚 research complete, he is now moving on to phase two.
鈥淲hat we鈥檙e moving onto now is studying the intracellular signaling pathways linked to cancer progression and investigating how these fluid stresses could activate a pathway that makes cells more metastatic or drug resistant,鈥� he said.
Overall, Landwehr has enjoyed using his engineering experience to make a difference, even if it鈥檚 just a small piece of the puzzle.
鈥淚t鈥檚 been really interesting to be able to combine chemical engineering principles to study biological systems, specifically cancer,鈥� he said. 鈥淭he thing with cancer research is that there鈥檚 not one real big breakthrough. I hope that our research will provide insight into further research.鈥�
Like us on (@lsuengineering) or follow us on and &苍产蝉辫;(蔼濒蝉耻别苍驳颈苍别别谤颈苍驳).鈥�
###
Contact: Libby Haydel
Communications Specialist
225-578-4840