Using single-cell to look into an under-studied area of cancer research, the stroma, to uncover the mechanisms behind prostate cancer metastasis

Biological Applications

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One of the Scipio bioscience grant winners, Assistant Professor Mohamed Omar at Weill Cornell Medicine, New York, USA, is planning to use his prize of Asteria™ kits worth $30,000 (including sequencing costs) to characterize the yet poorly understood diversity and dynamics in the cell types composing the stroma, the structure surrounding cancerous tumors.

Alongside Dr. Luigi Marchionni and Dr. Massimo Loda, also in the Department of Pathology and Laboratory Medicine at Weill Cornell Medicine, Dr. Omar is investigating the underlying mechanisms behind prostate cancer progression and metastasis, particularly how the tumor metastases to the nearby bones. Despite prostate cancer being a leading cause of death for men worldwide, previous decades of research focused on the tumor itself but rarely on the surrounding tissue, called stroma.

“The stroma has always been considered a supporting structure for the tumor, rather than an influential determinant factor for tumor progression and a cause of disease progression,” explains Dr. Omar. “This is an undiscovered area of research that we hope we can understand, for example how the stroma cell types, by interacting with the cancer cells, shape the tumor progression and metastasis and the survival of patients.”

Unearthing cell-cell communications thanks to single-cell

Over the past 50 years, it had always been assumed that stroma tissue was just one homogeneous unit made of fibroblasts in contrast to, for example, the diversity of the immune system cells. However, recent research has shown it was far from being the case.

“New studies, including our own, have reported the stroma to be much more heterogeneous than we previously thought,” continues Dr. Omar. “We discovered for example 8 distinctive stroma cell subtypes, each one with a different role towards mediating the tumor progression.”

This makes stroma tissue a prime sample to study at single-cell resolution, with the ability to distinguish specific pathways being activated in different fibroblasts subtypes thanks to differential gene expression. For Dr. Omar and his team, this is an opportunity to study the cell-cell interactions between stroma cells and the tumor. They plan to study the expression of specific ligands and receptors across the entire sample tissues and draw the dynamics leading to prostate cancer metastasis, for which a robust single-cell methodology would prove both essential and groundbreaking.

Dr. Omar confirms: “Single-cell is really making our life much better in helping to understand a lot more about the mechanisms underlying cancer progression and metastasis especially in prostate cancer.”

Looking for a single-cell solution that manages fresh, large, and fragile cells

A veteran of single-cell technologies, Dr. Omar has specific requirements for his current project which drew him to the sample preparation method offered by Scipio bioscience. One of those requirements is being able to minimize the use of compromises to access the RNA-seq data.

“Any artefacts that can affect the quality of the RNA, such as fixation techniques, would have a very detrimental effect on everything downstream, including the scientific conclusions,” Prof. Omar continues. “That’s why fresh samples will make our results authentic and more reliable and why we are very interested in using fresh samples instead of formalin-fixed, paraffin-embedded (FFPE) samples.”

With his team inferring the expression of certain ligands and receptors on different cell types to understand how certain cell types communicate with each other, this analysis is very sensitive to gene expression levels, which is in turn very sensitive to RNA quality. Using fresh samples would then minimize the impact of the sample preparation on the original transcriptome.

But using fresh samples is not the only reason Dr. Omar tuned to the Asteria scRNA-seq kit: the nature of his sample tissue required a method that could handle large and fragile cells and minimize the risk of cell death through mechanical pressure.

“In our analysis, certain cell types like stroma fibroblasts and certain immune system cells like macrophages are large and can be very fragile,” Dr. Omar clarifies. “Single-cell processing methods right now might lead to underrepresentation of those cell types due to their fragility; they do not pass the quality control criteria and we do not see them in the final data as I personally experienced. Somehow, this could skew our understanding of the tumor microenvironment as they hold crucial roles in tumor mediation. That’s why having a technology or kits that allow to maintain cell representation of fragile cells in our samples in extremely important.”

Thanks to hydrogel-based technology RevGel™ and its single-tube format, the Asteria™ scRNA-seq can handle fragile cells all the way to the lysis and mRNA capture process.

Dr. Omar’s research on this topic will be available on as his work progresses. To read about the other grant winners and their studies, you can head here, and here.