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Updated: Feb 20, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
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Induction of anti-VEGF therapy resistance by upregulated expression of microseminoprotein (MSMP)

T Mitamura1,2, S Pradeep1,3, M McGuire1

  • 1Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Oncogene
|October 24, 2017
PubMed

Insights

Microseminoprotein, prostate-associated (MSMP) drives resistance to anti-vascular endothelial growth factor (VEGF) therapy in ovarian cancer. Inhibiting MSMP may restore sensitivity to antiangiogenesis treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Anti-vascular endothelial growth factor (VEGF) therapies are effective against metastatic cancers but often face therapeutic resistance.
  • Understanding the tumor microenvironment's role is crucial for overcoming resistance to antiangiogenesis treatments.

Purpose of the Study:

  • To identify microenvironmental factors contributing to adaptive resistance in ovarian cancer treated with anti-VEGF therapy.
  • To explore microseminoprotein, prostate-associated (MSMP) as a potential mediator of this resistance.

Main Methods:

  • Genomic analysis of intraperitoneal ovarian tumors resistant to anti-VEGF therapy.
  • Investigated MSMP gene expression, secretion, and signaling pathways (MAPK) in cancer and endothelial cells.
  • Utilized MSMP siRNA delivered via nanoliposomes in vivo and measured serum MSMP levels in patients.

Main Results:

  • MSMP gene expression was significantly upregulated in resistant tumors.
  • Hypoxia induced MSMP secretion, promoting endothelial cell tube formation via MAPK signaling.
  • MSMP inhibition using siRNA restored tumor sensitivity to anti-VEGF therapy.
  • Elevated serum MSMP levels correlated with non-response to bevacizumab in ovarian cancer patients.

Conclusions:

  • MSMP is a key factor in developing resistance to anti-VEGF therapy in ovarian cancer.
  • Targeting MSMP in combination with antiangiogenesis drugs presents a novel strategy to overcome therapeutic resistance.

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