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Expression of Periostin Alternative Splicing Variants in Normal Tissue and Breast Cancer.

Yuko Kanemoto1, Fumihiro Sanada2, Kana Shibata3

  • 1Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Suita 565-0871, Japan.

Biomolecules
|September 28, 2024
PubMed
Summary

Periostin alternative splicing variants (ASVs) with exon 21 are elevated in breast cancer, acting as potential diagnostic and therapeutic targets. Targeting these variants shows promise in suppressing tumor growth.

Keywords:
alternative splicing variantsbreast cancerextracellular matrix proteinperiostin

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Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Periostin (Pn) is an extracellular matrix protein with physiological roles in bone formation and wound healing.
  • Aberrant Pn alternative splicing variants (ASVs) are implicated in breast cancer and heart failure pathogenesis.
  • The differential expression of Pn-ASVs in physiological versus pathological conditions remains unclear.

Purpose of the Study:

  • To investigate the expression patterns of Pn-ASVs in normal and breast cancer tissues.
  • To assess the potential of pathologically expressed Pn-ASVs as diagnostic and therapeutic targets for breast cancer.

Main Methods:

  • Examined Pn-ASVs expression in human breast cancer and adjacent normal tissues.
  • Utilized in situ hybridization to localize Pn-ASV synthesis.
  • Performed in vivo bio-distribution studies with a 89Zr-labeled Pn antibody targeting exon 21 (Pn-21Ab) in mice.
  • Assessed the therapeutic efficacy of Pn-21Ab in a mouse breast cancer model.

Main Results:

  • Physiologically expressed Pn isoforms predominantly lacked exons 17 and 21.
  • Pn-ASVs containing exon 21 were significantly upregulated in breast tumor tissues compared to normal adjacent tissues.
  • In situ hybridization revealed Pn-ASVs with exon 21 are synthesized in peri-tumoral stromal cells.
  • 89Zr-labeled Pn-21Ab showed selective tumor accumulation in vivo and suppressed tumor growth in mice.

Conclusions:

  • Pn-ASVs, particularly those with exon 21, are significantly altered in breast cancer.
  • These Pn-ASVs represent promising biomarkers for breast cancer diagnosis.
  • Targeting Pn-ASVs with exon 21 offers a potential therapeutic strategy for breast cancer.