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Updated: Feb 3, 2026

Electrochemotherapy of Tumours
03:57

Electrochemotherapy of Tumours

Published on: December 15, 2008

25.1K

Targeting SPINK1 in the damaged tumour microenvironment alleviates therapeutic resistance

Fei Chen1, Qilai Long2, Da Fu3

  • 1Key Laboratory of Tissue Microenvironment and Tumour, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.

Nature Communications
|October 19, 2018
PubMed

Insights

Chemotherapy damage induces SPINK1, a protein that fuels cancer growth and resistance. SPINK1 is a novel biomarker for monitoring treatment effects in the tumor microenvironment (TME).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Cancer therapies like chemotherapy and radiation damage tumor microenvironment (TME) stromal cells.
  • This damage induces a senescence-associated secretory phenotype (SASP), releasing soluble factors.
  • The SASP contributes to cancer progression and treatment resistance.

Purpose of the Study:

  • To identify and characterize novel SASP factors.
  • To investigate the role of SPINK1 in cancer aggressiveness and chemoresistance.
  • To evaluate SPINK1 as a biomarker for TME damage and patient surveillance.

Main Methods:

  • Investigated SPINK1 expression in human stromal cells post-genotoxic treatment.
  • Utilized molecular biology techniques to identify signaling pathways (NF-κB, C/EBP) regulating SPINK1.
  • Assessed the effects of SPINK1 on cancer cell aggressiveness, chemoresistance, and epithelial-endothelial transition (EET) in vitro and in vivo.
  • Detected SPINK1 in tumor stroma and patient peripheral blood.

Main Results:

  • Identified serine protease inhibitor Kazal type I (SPINK1) as a novel SASP factor.
  • Demonstrated that DNA damage induces SPINK1 via NF-κB and C/EBP signaling.
  • Showed that paracrine SPINK1 enhances cancer cell aggressiveness and chemoresistance.
  • Revealed that SPINK1 reprograms cancer cells, inducing EGFR-mediated epithelial-endothelial transition (EET).
  • Confirmed SPINK1 expression in solid tumor stroma and its presence in peripheral blood post-chemotherapy.

Conclusions:

  • SPINK1 is a key SASP factor promoting cancer aggressiveness and chemoresistance.
  • SPINK1 induces epithelial-endothelial transition (EET) in cancer cells.
  • SPINK1 serves as a targetable factor within the TME.
  • SPINK1 is a promising noninvasive biomarker for assessing TME damage and for clinical surveillance in cancer patients.

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