5 things spatial transcriptomics reveals about cancer cells

Over the past few a long time, scientists have discovered quite a few mechanisms for cancer cells to avoid cellular checkpoints. Several discoveries lately indicate that increasing FosB protein levels is a key mechanism of tumor metastasis and survival.

Nonetheless, existing transcriptome studies of cancer cells don’t have in mind dynamic changes in gene expression. Spatial transcriptomics, or spatial gene expression, is a brand new method that enables researchers to concurrently study gene expression in each cell in a sample, moderately than the common expression of cells in each organ or tissue. In this fashion, spatial transcriptomics eliminates the necessity to average gene expression levels and allows researchers to capture unique elements of biology. Listed below are 5 things that spatial transcriptomics reveals about cancer cells.

1. Spatial transcriptomics reveals cancer invasion

By spatial transcriptomicsresearchers found that cancer cells display different gene expression profiles along the invasive front and inside non-cancerous tumors. Spatial differences in gene expression occurred on the single-cell level, while mean gene expression in cancer cells was not significantly different from non-cancerous cells. This means that genetic changes are more diverse than previously thought.

Spatial transcriptomics reveals a link between FosB and invasion. Higher FosB levels correlated with faster tumor growth rates, higher invasiveness, and poor patient survival. Furthermore, spatial transcriptomics indicates that FosB levels weren’t uniform across the invasion front. As an alternative, it peaked at the top of the invasion front. This provides evidence that cell-to-cell variability is a crucial aspect of tumor aggressiveness.

A spatial transcriptomic approach also revealed a correlation between FosB and MMP2 levels in cancer cells. As expected, high MMP2 levels correlated with invasive cell fronts and poor patient survival. Nonetheless, quantitative spatial transcriptomics indicates that invasive cancer cells have high eukaryotic initiation factor 2 alpha (eIF2α) at ​​their forefront.

2. Spatial transcriptomics reveals tumor heterogeneity

Spatial transcriptomics found that cancer cells at different stages of malignancy exhibited unique gene expression profiles in a single biopsy sample taken from patients. This heterogeneity was reflected in a big selection of genes, including cell surface receptors, adhesion molecules, and growth aspects, which have been linked to cancer progression.

Spatial transcriptomics data show that several highly expressed genes answerable for tumorigenicity of cancer cells usually are not actively expressed on the invasive front. For instance, high levels of MMP9 were only present in cancer cells and never in leading invasive tumors. This implies that different stages of cancer are characterised by unique gene expression profiles and provides evidence that in invasive tumors, tumor cells have stem-like capabilities.

Spatial transcriptomics reveals that cancer cells showed increased expression of several metastasis-related genes. Cancer cells on the invasive front were also more motile than those present in noncancerous tumors. Spatial transcriptomics also uncovers significant differences in gene regulation between invasive and noninvasive cancer cells.

3. Spatial transcriptomics reveals the dynamic nature of cancer metabolism

Spatial transcriptomic data reveals the dynamic nature of tumor metabolism, with unique metabolite signatures for various tumor stages. Cells on the invasion front showed increased expression of several genes related to oxidative phosphorylation, cellular respiration, and amino acid metabolism and decreased levels of genes related to glycolysis. This implies that cancer cells on the invasive front are metabolically more aggressive than those in noncancerous tumors.

Cancer cells in noncancerous tumors showed increased levels of several genes related to ubiquitin-dependent proteolysis and autophagy. Along with being a metabolic process that degrades damaged proteins, it also has to do with the turnover of short-lived proteins akin to transcription aspects. This is especially vital within the case of metastasis, where cancer cells must undergo extensive changes in gene expression to change into motile and invasive.

4. Spatial transcriptomics reveals the importance of inducible protein synthesis and epigenetic regulation

Spatial transcriptomics reveals significant differences in protein synthesis between invasives Cancer cells and people inside non-cancerous tumors. Cancer cells on the invasive front showed increased expression of several proteins required for inducible protein synthesis, akin to phosphoinositide 3-kinase (PI3K) and ribosomal S6 P70 kinase (S6K) and proteins involved in chromatin remodeling.

Then again, invasive cancer cells showed reduced expression of p53, a protein essential for DNA repair and cell cycle arrest. Spatial transcriptomics also reveals that invading tumors showed decreased expression of histone deacetylase (HDAC) and a number of other lysine/arginine methyltransferases (K/R). The hypomethylated chromatin profile in invasive tumors may explain why spatial transcriptomics detected reduced expression of FosB and its downstream targets in these tumor cells. This means that epigenetic regulation could also be a crucial a part of cancer progression, as this dysregulation occurs even within the earliest stages of tumorigenesis.

Spatial transcriptomics reveals distinct differences in protein synthesis between invasive and noninvasive cancers. On the invasion front, it was also shown that there was increased expression of several genes involved in ribosome biogenesis, translation, and kinases. A lot of these proteins and kinases are regulated by p53, which was significantly downregulated. Spatial transcriptomics also reveals that many proteins involved in chromatin remodeling were present on the invasion front. These proteins included several histone deacetylases and lysine methyltransferases.

5. Spatial transcriptomics reveals the importance of cell-cell communication

Spatial transcriptomics reveals that genetic differences between individual cancer cells cannot explain spatial heterogeneity. As an alternative, they found that cell-to-cell variability was a key consider determining the tumor’s aggressiveness and progression. For instance, many soluble aspects were highly expressed on the invasive front, including lymphotoxin beta receptor and macrophage migration inhibitory factor. These molecules have been linked to cancer progression.

Just as spatial transcriptomy has detected significant differences in gene expression between cells at different stages of cancer, it has also identified the importance of cell-cell signaling in cancer progression. Spatial transcriptomics showed that the invasive front showed increased expression of several proteins related to cell-to-cell communication, including c-Met and cAMP response element binding protein (CREB).

Spatial transcriptomics uses a novel methodology to investigate human and mouse tissue samples from patients with invasive cancer. This platform represents a big advance in cancer research and has revealed vital information on the evolution of invasive tumors and their relationship with tumor progression.

Spatial transcriptomics has provided latest insights into how cancer cells change gene expression as they progress from noninvasive to invasive tumors. It has also been shown that multiple aspects, including differences in protein synthesis and cell-cell communication, could also be answerable for spatial heterogeneity inside the same tumor.

Application

The spatial transcriptomics platform has provided latest insight into cancer evolution and increased our understanding of how cancer cells change into more aggressive. Further research is required to analyze the role of intercellular signaling in cancer progression and to find out why some cancers display stable invasive fronts while others have dynamic fronts. A mirrored image on a decade of spatial transcriptomics research and its impact on basic and translational research within the human health sciences wouldn’t be complete without acknowledging several milestones which have been achieved during this era.