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Low RECK Expression Is Part of the Cervical Carcinogenesis Mechanisms

Suellen Herbster1, Marina Trombetta-Lima2, Paulo Thiago de Souza-Santos3

  • 1Laboratory of Oncovirology, Department of Microbiology, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-900, Brazil.

Cancers
|June 2, 2021
PubMed

Insights

Reversion-inducing Cysteine-rich protein with Kazal motifs (RECK) suppresses human papillomavirus (HPV) cervical cancer. Increased RECK expression reduced tumor growth and improved survival, while its loss correlates with disease progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Human papillomavirus (HPV) infection is a primary cause of cervical cancer.
  • Matrix metalloproteinases (MMPs) and their regulators, like RECK, are implicated in cancer development.
  • RECK typically inhibits MMP activity and is often downregulated in human cancers.

Purpose of the Study:

  • To investigate the role of RECK in cervical carcinogenesis.
  • To analyze the impact of RECK overexpression on tumor growth, immune response, and molecular characteristics in vivo.
  • To assess RECK expression levels in clinical cervical cancer samples.

Main Methods:

  • Overexpression of RECK in cervical cancer cell lines.
  • In vivo tumor growth and survival studies in a mouse model.
  • Analysis of tumor cell viability, endothelial cell proliferation, collagenase activity, and immune cell infiltration.
  • Examination of RECK mRNA levels in patient-derived cervical lesions and correlation with disease progression and chemotherapy response.

Main Results:

  • RECK overexpression significantly delayed tumor growth and enhanced overall survival in vivo.
  • RECK-overexpressing tumors showed increased lymphoid-like inflammatory cells and reduced tumor and endothelial cell viability.
  • Lower RECK mRNA levels were associated with cervical lesion progression and poorer chemotherapy outcomes in patients.

Conclusions:

  • Increased RECK expression diminishes the tumorigenic potential of HPV-transformed cells.
  • RECK downregulation is a significant event in cervical cancer progression and is linked to clinical outcomes.
Keywords:
HPVMMP inhibitorsRECKcervical cancertumorigenesis

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