Líf - og heilbrigðisvísindaráðstefna Háskóla Íslands 2021

The transforming potential of HER2 in sub-populations of breast epithelium

Main author: Hildur Rún Helgudóttir
Institution or Company: Læknadeild, Háskóli Íslands

Co-Author, Institution or Company:
Sævar Ingþórsson, Hjúkrunarfræðideild, Háskóli Íslands.

Introduction: Breast cancers are categorized based on key marker proteins, such as estrogen receptor or the receptor HER2. 30% of breast cancers are HER2 positive showing HER2 amplification and high expression. Tumors exhibiting HER2 amplification have worse prognosis than the hormone receptor positive tumors.

Methods: In this study, primary breast epithelial cells were used and the HER2 receptor overexpressed using lentiviral vectors, in both unsorted cells and cells sorted into sub-populations of breast epithelial cells using FACS. Cell lines such as SI28(basal) and D382(luminal) were also used as a comparison.

Results: Overexpression of HER2 was successful and in the unsorted primary cells the cells showed high heterogeneity relative to marker expression, such as KRT14, KRT19, MUC-1 and EpCAM. All cells formed similar spheroid structures when cultured in 3D culture.

We successfully isolated basal cells(CD49fhigh/EpCAMneg/CD10+) with FACS and overexpressed HER2. The cells showed similar morphology and did not branch in three-dimensional culture.

When cultured in 3D, SI28 is able to form branching structures whereas D382 form circular spheroids. With overexpression of HER2, SI28 loses its ability to form these branching structures and forms circular spheroids. SI28 HER2 shows pattern of more invasion and migration. D382 shows no morphological changes. In addition, metabolic changes were observed, as evidenced by the acidification of the media.

Conclusion: HER2 has an impact on the morphogenic potential of the cells, via loss of spatial orientation and metabolism. This observation needs further study and is currently being analyzed.

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