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Glypican-1 Level Is Elevated in Extracellular Vesicles Released from MC38 Colon Adenocarcinoma Cells Overexpressing
Izabela Papiewska-Pająk1, Damian Krzyżanowski1, Maria Katela2
1Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland.
Abstract:
The transcription factor Snail triggers epithelial-to-mesenchymal transition (EMT), endowing cancer cells with invasive properties during tumor progression. Extracellular vesicles (EVs) released from cancer cells at various stages of cancer progression are known to influence the tumor pre-metastatic niche and metastatic potential. The aim of this study was to analyze the effect of Snail on murine colon adenocarcinoma cells (MC38 line) and on the characteristics of their EVs. Stable clones of Snail-overexpressing MC38 cells were investigated in vitro versus Mock cells. Increased expression of matrix metalloproteinase MMP-14 and augmented activity of MMP-9 and -14 were observed in Snail-MC38 cells. There was no change in the transcriptomic profile of proteoglycans in Snail-MC38 cells; however, the protein level of Glypican-1 (GPC1) was enhanced in EVs released from those cells. Our finding that GPC1 protein level was enhanced in EVs released from MC38 cells that overexpressed Snail and were in an early EMT stage might explain the specificity of the GPC1 biomarker in colon cancer diagnosis. Further, our data suggest that Snail, by changing the level of GPC1 on EVs released by colon cancer cells, may affect the generation of a distant premetastatic niche and metastatic organotropism in colon adenocarcinoma.
Insights
The transcription factor Snail promotes cancer cell invasion and alters extracellular vesicles (EVs). Overexpressing Snail in colon cancer cells increases Glypican-1 (GPC1) in EVs, potentially impacting metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The transcription factor Snail drives epithelial-to-mesenchymal transition (EMT), enhancing cancer cell invasiveness.
- Extracellular vesicles (EVs) from cancer cells modulate the pre-metastatic niche and metastatic potential.
- Understanding Snail's role in EV modification is crucial for cancer progression insights.
Purpose of the Study:
- To investigate the impact of Snail overexpression on murine colon adenocarcinoma MC38 cells.
- To analyze alterations in the characteristics of EVs released from Snail-modified MC38 cells.
- To explore the potential role of Glypican-1 (GPC1) in Snail-mediated EV changes and colon cancer metastasis.
Main Methods:
- Generation of stable Snail-overexpressing MC38 cell clones.
- In vitro comparison of Snail-MC38 cells with Mock control cells.
- Analysis of matrix metalloproteinase (MMP) expression and activity.
- Transcriptomic profiling of proteoglycans and protein analysis of EVs, focusing on GPC1.
Main Results:
- Snail-MC38 cells exhibited increased matrix metalloproteinase MMP-14 expression and MMP-9/-14 activity.
- No significant changes in proteoglycan transcriptomic profiles were observed.
- Enhanced Glypican-1 (GPC1) protein levels were detected in EVs from Snail-overexpressing MC38 cells.
Conclusions:
- Snail overexpression in colon cancer cells leads to elevated GPC1 levels in released EVs.
- This Snail-induced GPC1 alteration in EVs may influence pre-metastatic niche formation and organotropism.
- GPC1 in EVs from Snail-expressing cells could serve as a specific biomarker for colon cancer diagnosis.
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