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In Vitro Evaluation of Oncogenic Transformation in Human Mammary Epithelial Cells
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The Use of Human Serum Samples to Study Malignant Transformation: A Pilot Study
Andreana N Holowatyj1,2,3,4, Biljana Gigic5, Christy A Warby3,4
1Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Cells
|October 23, 2021
Summary
Human serum can promote cancerous cell growth, but fibroblast growth factor-2 (FGF2) levels are not directly linked. The FGF2/FGFR1 pathway is implicated in this malignant transformation process.
Area of Science:
- Oncology
- Biochemistry
- Cell Biology
Background:
- Obesity is linked to ~20% of cancers, yet cancer risk biomarkers are not fully understood.
- Fibroblast growth factor-2 (FGF2) is a potential biomarker for visceral adipose tissue, but its role in cancer development is unclear.
- Discovering functional biomarkers for cancer risk is challenging.
Purpose of the Study:
- To investigate if human serum can induce 3D growth in non-tumorigenic cells, a marker of cancerous transformation.
- To explore the association between circulating FGF2 levels and malignant transformation in vitro.
- To identify key serum factors involved in promoting tumorigenesis.
Main Methods:
- Utilized soft agar assays to measure anchorage-independent growth of JB6 P+ epithelial cells stimulated by human serum.
- Conducted a pilot study analyzing serum FGF2 levels in 33 men and women.
- Assessed the effect of a fibroblast growth factor receptor-1 (FGFR1) inhibitor on serum-stimulated cell transformation.
Main Results:
- Human serum from healthy individuals stimulated the 3D growth of non-tumorigenic epithelial cells in soft agar.
- Serum FGF2 levels did not correlate with epithelial cell colony formation (r=0.05, p=0.80).
- A selective FGFR1 inhibitor significantly reduced serum-induced cell transformation, indicating FGF2/FGFR1 pathway involvement.
Conclusions:
- The FGF2/FGFR1 axis appears to play a role in JB6 P+ cell malignant transformation.
- Human serum contains factors that can promote tumorigenesis in epithelial cells.
- Developed a novel assay for identifying serum factors that drive cancer development.

