How Do Stem Cells Interact With Breast Cancer Cells?

Researchers have investigated how human mesenchymal stem cells (hMSCs) and breast cancer cells interact and affect each other’s invasiveness – a concept that has previously left scientists puzzled.

hMSCs are found in bone marrow and are important for regenerating and repairing damaged areas in the body as they can differentiate into a variety of cell types, including those that make bone, cartilage, muscle and fat.

Cancer researchers have turned their focus to hMSCs as they naturally travel to tumors when they appear in the body and interact with cancer cells.

They are particularly keen to understand if hMSCs can interact with cells to prevent "secondary breast cancer" as this type of cancer is incurable.

Secondary breast cancer occurs when cancer cells from a primary tumor in the breast spread to nearby tissues such as the lungs, bones and liver via the blood or lymphatic system – a process known as "metastasis".

Though hMSCs are naturally drawn to these “invasive” cancer cells, how the cells interact and affect each other is unclear and previous research projects are divided in their results, with some finding hMSCs promote metastasis and others concluding they reduce it.

The study focused on MDA-MB-231 – a type of breast cancer cell line that is known for being extremely invasive.

The research found that hMSCs dramatically reduce the invasiveness of MDA-MB-231 breast cancer cells. However, this research is different to previous studies, in that it used a 3D model.

Most scientists look at how cancers interact with cells by either growing tumors in mice or by using 2D monolayer cultures – cells that are grown in a dish, flat and side-by-side, under controlled conditions.

Growing cancers in the body (in vivo) of mice is not representative of what happens in humans due to differences in the microenvironment, and the 2D models also have their limitations as tumors are not flat, they are 3D and touch cells that are all around them, not just those to the sides of it.

Dr Mhairi Morris, who co-authored the study, describes it, modelling tumors in 2D is like “playing football lying on the ground side-by-side – possible, but rubbish”.

Modelling cancer in 3D allows researchers to see how cancer cells interact with all cell surfaces they come into contact with, giving a more accurate picture of what happens inside the human body.

Under the guidance of Dr Morris and also Loughborough’s Dr Liz Akam, an expert in hMSCs, doctoral student Mj Brown developed a 3D model that allowed her to explore the relationship between hMSCs and MDA-MB-231 breast cancer cells.

Brown created 3D spherical tumors by mixing (“co-culturing”) hMSC cells with the cancer cells and suspending them from the lid of a tissue culture dish.

Once the “spheroids” were formed, they were embedded into the jelly-like matrix that mimics the environment breast cancer cells would be in inside the body.

Changes of invasiveness were observed over a five-day period by measuring the length of the projections the cells put out into the matrix – a known measure of cell invasion – and it was found the cancer cells became less invasive when mixed with the hMSCs.

The results provide new evidence for how cancer cells and stem cells interact in the body and further highlights the effectiveness of 3D models.

The research is also important for scientists working in the field as, while determining the optimum co-culture conditions to create the spheroids, Brown found the source of serum – a supplement added to the cell culturing media, which contains a mixture of necessary proteins, hormones and other growth factors that aid cell growth – had a significant effect on the growth of the cells investigated.

Brown said of the study: “Continuing to investigate the interaction between hMSCs and cancer cells in 3D systems is now essential to further understanding this relationship and the impact of the tumor microenvironment on metastasis.

“Using 3D models such as the one used in this study provides an opportunity for in vitro relationships to be investigated and novel research on the mesenchymal stem cell-driven biochemical modulation of breast cancer cell metastases to be conducted.

“I hope my research enables us to further understand the relationship between hMSCs and breast cancer cells in order to develop new therapeutic methods to prevent breast cancer metastases.”

Brown is already building on this research, investigating the role that exercise has on the relationship between hMSCs and breast cancer cells and whether physical activity could reduce invasiveness even further.

“The future of in vitro modelling is in three – or more! – dimensions and we’re excited to be bringing our unique spin on this – co-culturing breast cancer cells with hMSCs and seeing what effect exercise may have on this interaction.” concluded Dr Morris.

Reference

Brown et al. (2020) Determining Conditions for Successful Culture of Multi-Cellular 3D Tumour Spheroids to Investigate the Effect of Mesenchymal Stem Cells on Breast Cancer Cell Invasiveness. Bioengineering. DOI: https://doi.org/10.3390/bioengineering6040101

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