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Basic Science

Poster Session 4

(976) Pregnancy related extracellular vesicles induce breast cancer cell migration and proliferation

Wednesday, February 14, 2024
1:00 PM – 2:30 PM  
Location: Prince George's Exhibit Hall CDE, Lower Atrium Level
Objective:

Pregnancy-associated breast cancer (PABC) is associated with an aggressive disease and shorter survival, indicating that pregnancy itself may promote cancer progression through unidentified mechanisms.

Extracellular vesicle (EVs) are lipid membrane vesicles involved in both tumor progression and modulation of the immune system in cancer as well as induction of angiogenesis in pregnancy. EVs may support cancer growth by inducing immunosuppression and creating a conducive pre-cancerous niche.

Placental EVs compose ~10% of the EV population in pregnant women. The placenta and malignant tumors share several properties, including a high rate of tissue proliferation, invasion, angiogenesis, and immune modulation. We propose a model whereby EVs that normally mediate placental-maternal crosstalk can also promote the aggressive nature of PABC. The study aimed to explore the effects of pregnancy-related EVs on breast cancer cell growth.

Study Design:

EVs obtained from placental human villous trophoblast cells (HVT) and EVs obtained from plasma of healthy pregnant (HP) and non-pregnant (NP) women were isolated and incubated with target cells. The effects of placental HVT-EVs or pregnancy related EVs on breast cancer cell lines MCF7, luminal (ER+, PR+) and MDA-231, triple negative aggressive cell lines and their related cancer stem cells (CSC), isolated by FACS sorting of ALDH+CD24-CD44+ cells, were compared to the response of a benign cell line, MCF10a. The effects of EVs on cell proliferation and migration were assessed.

Results:

Co-culture of placental EVs (HVT-EVs or HP-EVs) with BC cell lines increased migration of MCF7 cells, MDA-231 cells and their related cancer stem cells compared to NP-EVs or untreated wells (Figure 1). 

MCF7 CSC and MDA-231 CSC show increased proliferation in XTT tests when exposed to HVT EVs or HP EVs compared to exposure to NP EVs or no EVs. This response was not evident in MCF10a benign breast cancer cells. 

Conclusion:

Pregnancy related extracellular vesicles may contribute to the aggressive nature of pregnancy-associated breast cancer.