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Selective down-regulation of integrin receptors in spheroids of squamous cell carcinoma

N S Waleh1, J Gallo, T D Grant

  • 1Cellular and Molecular Biology Laboratory, SRI International, Menlo Park, California 94025.

Cancer Research
|February 1, 1994
PubMed

Insights

Integrin expression, particularly alpha 6, beta 1, and beta 4 subunits, is reduced in A431 cell spheroids, mimicking in vivo patterns. Cell-cell contact and microenvironment significantly regulate integrin expression.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Integrins are crucial for cell-matrix interactions and cytoskeleton organization.
  • Integrin expression is often altered in squamous cell carcinomas.
  • A431 cell line serves as a model for studying epithelial cell behavior.

Purpose of the Study:

  • To investigate integrin expression in A431 cells grown as multicellular spheroids versus monolayers.
  • To determine the effect of cell-cell contact and microenvironment on integrin expression.
  • To examine the role of epidermal growth factor (EGF) in regulating integrin expression.

Main Methods:

  • Culturing A431 cells as monolayers and multicellular spheroids of varying sizes.
  • Immunostaining using monoclonal antibodies for specific integrin subunits (alpha 6, beta 1, beta 4, alpha 2).
  • Western blot analysis for protein levels and Northern blot analysis for mRNA transcripts of integrins.

Main Results:

  • Integrin subunits alpha 6, beta 1, and beta 4 showed reduced expression in spheroids compared to monolayers, at both protein and mRNA levels.
  • Alpha 2 integrin expression remained uniform, while alpha v showed slight reduction in spheroids.
  • Epidermal growth factor (EGF) upregulated mRNA expression of alpha 2, alpha 6, beta 1, and beta 4 integrins in both cell types.

Conclusions:

  • Cell-cell contact and the spheroid microenvironment regulate the expression and distribution of specific integrin subunits.
  • The observed integrin expression patterns in spheroids closely resemble those found in vivo in squamous cell carcinomas.
  • EGF plays a role in modulating integrin expression, suggesting its involvement in tumor growth and progression.

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