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Integrin α3β1 on Tumor Keratinocytes Is Essential to Maintain Tumor Growth and Promotes a Tumor-Supportive

Whitney M Longmate1, Scott Varney1, Derek Power1

  • 1Department of Surgery Albany Medical College, Albany, New York, USA.

The Journal of Investigative Dermatology
|May 27, 2020
PubMed

Insights

Integrin alpha3beta1 (α3β1) is crucial for maintaining skin tumors. Removing α3β1 causes established tumors to regress by affecting both tumor cells and their microenvironment, revealing it as a potential therapeutic target.

Area of Science:

  • Oncology
  • Dermatology
  • Cell Biology

Background:

  • Integrin function in cancer is not fully understood, hindering targeted therapies.
  • Previous studies suggest integrin α3β1 promotes skin tumor formation.
  • The role of α3β1 in established tumors and their microenvironment requires further investigation.

Purpose of the Study:

  • To investigate the role of integrin α3β1 in maintaining established skin tumors and the tumor microenvironment.
  • To determine if α3β1 is essential for tumor cell survival or stromal support.
  • To identify specific molecular pathways regulated by α3β1 in skin cancer.

Main Methods:

  • Generated tamoxifen-inducible, epidermis-specific α3 knockout mice.
  • Induced α3 gene ablation in established skin tumors.
  • Analyzed tumor regression, cell proliferation, apoptosis, and stromal changes.
  • Utilized mass spectrometry and RNA in situ hybridization to study the keratinocyte secretome.

Main Results:

  • Genetic ablation of α3 in established skin tumors led to rapid tumor regression.
  • Reduced tumor cell proliferation and increased apoptosis were observed, alongside significant stromal apoptosis.
  • Deletion of α3 reduced macrophage and fibulin-2 levels in the tumor stroma.
  • α3β1 was found to regulate the keratinocyte secretome, including fibulin-2 and macrophage CSF1.

Conclusions:

  • Integrin α3β1 is essential for the maintenance and growth of established skin tumors.
  • α3β1 plays a critical role in regulating the tumor microenvironment, particularly stromal cell survival and immune cell infiltration.
  • α3β1 is a key regulator of the keratinocyte secretome and represents a promising therapeutic target for skin cancer.

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