2. Academic Validation
  3. Epidermal growth factor receptor ligands enriched in follicular fluid exosomes promote oncogenesis of fallopian tube epithelial cells

Epidermal growth factor receptor ligands enriched in follicular fluid exosomes promote oncogenesis of fallopian tube epithelial cells

  • Cancer Cell Int. 2024 Dec 21;24(1):424. doi: 10.1186/s12935-024-03614-9.
Aye Aye Khine 1,  Pao-Chu Chen 2,  Ying-Hsi Chen 2,  Sung-Chao Chu 3 4,  Hsuan-Shun Huang 5,  Tang-Yuan Chu 6 7 8 9
Affiliations

Affiliations

  • 1 Center for Prevention and Therapy of Gynecological Cancers, Department of Research, Hualien, 970, Taiwan, ROC.
  • 2 Department of Obstetrics & Gynecology, Buddhist Tzu Chi General Hospital, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, 970, Taiwan, ROC.
  • 3 Department of Hematology and Oncology, Hualien, 970, Taiwan, ROC.
  • 4 School of Medicine, College of Medicine, Hualien, 970, Taiwan, ROC.
  • 5 Center for Prevention and Therapy of Gynecological Cancers, Department of Research, Hualien, 970, Taiwan, ROC. huang.sansam@gmail.com.
  • 6 Center for Prevention and Therapy of Gynecological Cancers, Department of Research, Hualien, 970, Taiwan, ROC. hidrchu@gmail.com.
  • 7 Department of Obstetrics & Gynecology, Buddhist Tzu Chi General Hospital, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, 970, Taiwan, ROC. hidrchu@gmail.com.
  • 8 School of Medicine, College of Medicine, Hualien, 970, Taiwan, ROC. hidrchu@gmail.com.
  • 9 Institute of Medical Science, Tzu Chi University, Hualien, 970, Taiwan, ROC. hidrchu@gmail.com.
PMID: 39709453 DOI: 10.1186/s12935-024-03614-9
Abstract

Background: Incessant ovulation is the main etiologic factor of ovarian high-grade serous carcinomas (HGSC), which mostly originate from the fallopian tube epithelium (FTE). Receptor tyrosine kinase (RTK) ligands essential for follicle development and ovulation wound repair were abundant in the follicular fluid (FF) and promoted the transformation of FTE cells. This study determined whether RTK ligands are present in FF exosomes and whether epidermal growth factor receptor (EGFR) signaling is essential for oncogenic activity.

Methods: The FF of women undergoing in vitro fertilization was fractionated based on the richness of exosomes and tested for transformation toward FTE cells under different RTK inhibitors. EGFR ligands in FF exosomes were identified, and downstream signaling proteins in FTE cells were characterized.

Results: The transforming activity of FF was almost exclusively enriched in exosomes, which possess a high capacity to induce anchorage-independent growth, clonogenicity, migration, invasion, and proliferation of FTE cells. EGFR inhibition abolished most of these activities. FF and FF exosome exposure markedly increased EGFR phosphorylation and the downstream signal proteins, including Akt, MAPK, and FAK. Multiple EGF family growth factors, such as Amphiregulin, Epiregulin, Betacellulin, and transforming growth factor-alpha, were identified in FF exosomes.

Conclusions: Our results demonstrate that FF exosomes serve as carriers of EGFR ligands as well as ligands of Other RTKs that mediate the transformation of FTE cells and underscore the need to further explore the content and roles of FF exosomes in HGSC development.

Keywords

Epidermal growth factor receptor (EGFR); Follicular fluid (FF); High-grade serous carcinomas (HGSC); Ovulation; exosome.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-10374
    99.96%, Flk-1/KDR抑制剂
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z