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Updated: Jun 23, 2026

Quantification of Breast Cancer Cell Invasiveness Using a Three-dimensional (3D) Model
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Quantification of Breast Cancer Cell Invasiveness Using a Three-dimensional (3D) Model

Published on: June 11, 2014

ERBB1 and ERBB2 have distinct functions in tumor cell invasion and intravasation

Dmitriy Kedrin1, Jeffrey Wyckoff, Pamela J Boimel

  • 1Department of Anatomy and Structural Biology and Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, New York, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|May 22, 2009
PubMed
Abstract

Insights

Epidermal growth factor receptor (EGFR) and HER2 inhibition rapidly blocks breast cancer cell invasion and intravasation. This study differentiates the roles of EGFR and HER2 in metastasis, suggesting ERBB inhibition for broader anti-cancer strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metastasis

Background:

  • Epidermal growth factor receptor (EGFR, also known as ERBB1) and HER2 (ERBB2) are frequently overexpressed in aggressive breast cancers, correlating with poor patient prognosis.
  • While ERBB inhibitors are studied for tumor growth effects, ERBBs can promote malignancy independently of tumor growth.
  • ERBB signaling pathways play a critical role in cancer cell invasion and metastasis.

Purpose of the Study:

  • To investigate the effect of ERBB1 and ERBB2 inhibition on in vivo tumor cell motility and intravasation using clinically relevant small-molecule inhibitors.
  • To evaluate the potential of ERBB inhibitors in blocking key steps of cancer cell metastasis beyond tumor growth.

Main Methods:

  • Utilized in vivo mouse models of breast cancer, specifically mammary fat pad tumors.
  • Tested the effects of ERBB1 and ERBB2 inhibitors, including AC480, lapatinib, gefitinib (ERBB1 inhibitor), and AG825 (ERBB2 inhibitor), on tumor cell invasive properties.

Main Results:

  • Inhibition of both ERBB1 and ERBB2 rapidly suppressed tumor cell motility and intravasation within 3 hours.
  • ERBB1 inhibition (gefitinib) effectively reduced tumor cell motility and invasion but not intravasation.
  • ERBB2 inhibition (AG825) specifically and rapidly blocked intravasation.

Conclusions:

  • ERBB1 and ERBB2 inhibition demonstrate rapid efficacy in blocking critical tumor cell invasive properties.
  • This study provides the first differentiation of ERBB1 and ERBB2 contributions to in vivo tumor cell invasion and intravasation.
  • The findings suggest that ERBB inhibition can be a valuable strategy to impede cancer cell metastasis by targeting invasion and intravasation, in addition to tumor growth.

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