Development of a Folding Paper System To Enable the Analysis of Gene Profile of Short- and Long-Distance Cancer Cell Migration

In
cancer metastasis, where mortality rates remain high
despite
advancements in medical treatments, understanding the molecular pathways
and cellular dynamics underlying tumor spread is critical for devising
more effective therapeutic strategies. Here, a folding paper system
was proposed and developed to mimic native tumor microenvironment.
This system, composed of 7 stacked layers of paper enclosed in a holder,
allows for the culture of cancer cells under conditions mimicking
those found in solid tumors, including limited oxygen and nutrients.
Because of the migratory capabilities of cancer cells, the cells in
the center layer could migrated to outer layers of the paper stack,
enabling the differentiation of cells based on their migratory potential.
Subsequent gene expression analysis, conducted through RT-PCR and
RNA sequencing, revealed significant correlations between cancer cell
migration distance and the expression of genes associated with hypoxia,
metabolism, ATP production, and cellular process. Moreover, our study
identified cells with aggressive phenotypic traits from the outer
layers of the paper stack, highlighting the potential of this system
for enabling the study of aggressive cancer cell characteristics.
Validation of the folding paper system against clinical carcinoma
tissue demonstrated its ability to faithfully mimic the native tumor
microenvironment. Overall, our findings underscore the utility of
the folding paper system as a valuable tool for investigating and
identifying critical molecular pathways involved in cancer metastasis.