(1005) FGF2 interferes with EGF/EGFR pathway in trophoblasts

Friday, January 31, 2025

4:00 PM – 6:00 PM

Submitting Author and Presenting Author(s)

Colleen Sinnott, MD (she/her/hers)

Fellow
Yale University
New Haven, Connecticut, United States

Coauthor(s)

Olga Grechukhina, MD

Yale School of Medicine
New Haven, CT, United States
Viktoriia Kolesnyk, MD

Yale School of Medicine
New Haven, CT, United States
YY

Yang Yang-Hartwich, PhD

Yale School of Medicine
New Haven, Connecticut, United States

Objective: Trophoblast migration and invasion are critical to establishment of the healthy placenta, and dysregulation of these processes can result in placental disorders including placenta accreta spectrum (PAS) and preeclampsia (PEC) with high morbidity and mortality. We previously identified fibroblast growth factor-2 (FGF2) as a likely regulator of trophoblast migration. Further, we suggested that FGF2 may interact with epidermal growth factor (EGF) pathway, another signaling pathway that plays a key role in placenta biology. Here we aim to better characterize specific effects of FGF2 on EGF-mediated trophoblast function.

Study Design: Using immortalized human trophoblast cells (Sw.71), we performed transwell migration assay with human serum from healthy pregnant patients with and without a selective FGF2 neutralizing antibody. Next, trophoblasts were treated with either EGF alone or a combination of both EGF and FGF after which flow cytometry for surface expression of EGF receptor (EGFR) was performed. Western blot (WB) was then conducted to evaluate total EGFR expression after treatment with FGF2 and EGF individually and in combination.

Results: Blocking FGF2 in serum collected from healthy pregnant patients resulted in suppressed trophoblast migration. (Figure 1). Trophoblast exposure to EGF resulted in decrease in surface EGFR; however, combination treatment with FGF2 and EGF further decreased surface EGFR compared to treatment with EGF alone (Figure 2A). Similarly, EGF, but not FGF2, solo treatment resulted in decreased total levels of EGFR protein demonstrated by WB (Figure 2B). Combined treatment with FGF2 and EGF resulted in total EGFR expression most similar to EGF treatment alone.

Conclusion: FGF2 is not only critical to trophoblast migration but may also play a role in regulating the EGF/EGFR pathway in trophoblasts. The decreased surface expression of EGFR after co-treatment with both EGF and FGF2 compared to EGF alone suggests that FGF2 may control cell-surface recycling of EGFR, leaving cells less able to respond to EGF signaling.