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

Dmitriy Kedrin, Jeffrey Wyckoff, Pamela J. Boimel, Salvatore J. Coniglio, Nancy E. Hynes, Carlos L. Arteaga, Jeffrey E. Segall

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Purpose: The epidermal growth factor receptor (ERBB1) and related family member HER-2/neu (ERBB2) are often overexpressed in aggressive breast cancers and their overexpression is correlated with poor prognosis. Clinical studies using ERBB inhibitors have focused on tumor growth effects, but ERBBs can contribute to malignancy independent of their effects on tumor growth. Our studies were designed to evaluate the effect of ERBB inhibition on tumor cell motility and intravasation in vivo using clinically relevant small-molecule inhibitors. Experimental Design: Using in vivo mouse models of breast cancer, we test the effects of ERBB1 and ERBB2 inhibitors AC480 and lapatinib, ERBB1 inhibitor gefitinib, and ERBB2 inhibitor AG825 on in vivo tumor cell invasive properties in mammary fat pad tumors. Results: ERBB1 and ERBB2 inhibition rapidly (within 3 h) inhibits both tumor cell motility and intravasation. Using gefitinib, ERBB1 inhibition rapidly inhibits tumor cell motility and invasion but not intravasation, whereas ERBB2 inhibition by AG825 rapidly blocks intravasation. Conclusions: ERBB1 and ERBB2 inhibition can rapidly block tumor cell invasive properties. In addition, we differentiate for the first time the contributions of ERBB1 and ERBB2 to the key metastatic properties of in vivo tumor cell invasion and intravasation. These experiments temporally and molecularly separate two key stages in tumor cell entry into blood vessels: invasion and intravasation. These results indicate that ERBB inhibition should be considered for blocking other tumor cell malignant properties besides growth.

Original languageEnglish (US)
Pages (from-to)3733-3739
Number of pages7
JournalClinical Cancer Research
Volume15
Issue number11
DOIs
StatePublished - Jun 1 2009

Fingerprint

Neoplasms
Cell Movement
Growth
Breast Neoplasms
Epidermal Growth Factor Receptor
Blood Vessels
Inhibition (Psychology)
Adipose Tissue
Breast
Research Design
gefitinib
tyrphostin AG825

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kedrin, D., Wyckoff, J., Boimel, P. J., Coniglio, S. J., Hynes, N. E., Arteaga, C. L., & Segall, J. E. (2009). ERBB1 and ERBB2 have distinct functions in tumor cell invasion and intravasation. Clinical Cancer Research, 15(11), 3733-3739. https://doi.org/10.1158/1078-0432.CCR-08-2163

ERBB1 and ERBB2 have distinct functions in tumor cell invasion and intravasation. / Kedrin, Dmitriy; Wyckoff, Jeffrey; Boimel, Pamela J.; Coniglio, Salvatore J.; Hynes, Nancy E.; Arteaga, Carlos L.; Segall, Jeffrey E.

In: Clinical Cancer Research, Vol. 15, No. 11, 01.06.2009, p. 3733-3739.

Research output: Contribution to journalArticle

Kedrin, D, Wyckoff, J, Boimel, PJ, Coniglio, SJ, Hynes, NE, Arteaga, CL & Segall, JE 2009, 'ERBB1 and ERBB2 have distinct functions in tumor cell invasion and intravasation', Clinical Cancer Research, vol. 15, no. 11, pp. 3733-3739. https://doi.org/10.1158/1078-0432.CCR-08-2163
Kedrin, Dmitriy ; Wyckoff, Jeffrey ; Boimel, Pamela J. ; Coniglio, Salvatore J. ; Hynes, Nancy E. ; Arteaga, Carlos L. ; Segall, Jeffrey E. / ERBB1 and ERBB2 have distinct functions in tumor cell invasion and intravasation. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 11. pp. 3733-3739.
@article{c11026dc2d0948a7983b49a0f1dbb0fb,
title = "ERBB1 and ERBB2 have distinct functions in tumor cell invasion and intravasation",
abstract = "Purpose: The epidermal growth factor receptor (ERBB1) and related family member HER-2/neu (ERBB2) are often overexpressed in aggressive breast cancers and their overexpression is correlated with poor prognosis. Clinical studies using ERBB inhibitors have focused on tumor growth effects, but ERBBs can contribute to malignancy independent of their effects on tumor growth. Our studies were designed to evaluate the effect of ERBB inhibition on tumor cell motility and intravasation in vivo using clinically relevant small-molecule inhibitors. Experimental Design: Using in vivo mouse models of breast cancer, we test the effects of ERBB1 and ERBB2 inhibitors AC480 and lapatinib, ERBB1 inhibitor gefitinib, and ERBB2 inhibitor AG825 on in vivo tumor cell invasive properties in mammary fat pad tumors. Results: ERBB1 and ERBB2 inhibition rapidly (within 3 h) inhibits both tumor cell motility and intravasation. Using gefitinib, ERBB1 inhibition rapidly inhibits tumor cell motility and invasion but not intravasation, whereas ERBB2 inhibition by AG825 rapidly blocks intravasation. Conclusions: ERBB1 and ERBB2 inhibition can rapidly block tumor cell invasive properties. In addition, we differentiate for the first time the contributions of ERBB1 and ERBB2 to the key metastatic properties of in vivo tumor cell invasion and intravasation. These experiments temporally and molecularly separate two key stages in tumor cell entry into blood vessels: invasion and intravasation. These results indicate that ERBB inhibition should be considered for blocking other tumor cell malignant properties besides growth.",
author = "Dmitriy Kedrin and Jeffrey Wyckoff and Boimel, {Pamela J.} and Coniglio, {Salvatore J.} and Hynes, {Nancy E.} and Arteaga, {Carlos L.} and Segall, {Jeffrey E.}",
year = "2009",
month = "6",
day = "1",
doi = "10.1158/1078-0432.CCR-08-2163",
language = "English (US)",
volume = "15",
pages = "3733--3739",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "11",

}

TY - JOUR

T1 - ERBB1 and ERBB2 have distinct functions in tumor cell invasion and intravasation

AU - Kedrin, Dmitriy

AU - Wyckoff, Jeffrey

AU - Boimel, Pamela J.

AU - Coniglio, Salvatore J.

AU - Hynes, Nancy E.

AU - Arteaga, Carlos L.

AU - Segall, Jeffrey E.

PY - 2009/6/1

Y1 - 2009/6/1

N2 - Purpose: The epidermal growth factor receptor (ERBB1) and related family member HER-2/neu (ERBB2) are often overexpressed in aggressive breast cancers and their overexpression is correlated with poor prognosis. Clinical studies using ERBB inhibitors have focused on tumor growth effects, but ERBBs can contribute to malignancy independent of their effects on tumor growth. Our studies were designed to evaluate the effect of ERBB inhibition on tumor cell motility and intravasation in vivo using clinically relevant small-molecule inhibitors. Experimental Design: Using in vivo mouse models of breast cancer, we test the effects of ERBB1 and ERBB2 inhibitors AC480 and lapatinib, ERBB1 inhibitor gefitinib, and ERBB2 inhibitor AG825 on in vivo tumor cell invasive properties in mammary fat pad tumors. Results: ERBB1 and ERBB2 inhibition rapidly (within 3 h) inhibits both tumor cell motility and intravasation. Using gefitinib, ERBB1 inhibition rapidly inhibits tumor cell motility and invasion but not intravasation, whereas ERBB2 inhibition by AG825 rapidly blocks intravasation. Conclusions: ERBB1 and ERBB2 inhibition can rapidly block tumor cell invasive properties. In addition, we differentiate for the first time the contributions of ERBB1 and ERBB2 to the key metastatic properties of in vivo tumor cell invasion and intravasation. These experiments temporally and molecularly separate two key stages in tumor cell entry into blood vessels: invasion and intravasation. These results indicate that ERBB inhibition should be considered for blocking other tumor cell malignant properties besides growth.

AB - Purpose: The epidermal growth factor receptor (ERBB1) and related family member HER-2/neu (ERBB2) are often overexpressed in aggressive breast cancers and their overexpression is correlated with poor prognosis. Clinical studies using ERBB inhibitors have focused on tumor growth effects, but ERBBs can contribute to malignancy independent of their effects on tumor growth. Our studies were designed to evaluate the effect of ERBB inhibition on tumor cell motility and intravasation in vivo using clinically relevant small-molecule inhibitors. Experimental Design: Using in vivo mouse models of breast cancer, we test the effects of ERBB1 and ERBB2 inhibitors AC480 and lapatinib, ERBB1 inhibitor gefitinib, and ERBB2 inhibitor AG825 on in vivo tumor cell invasive properties in mammary fat pad tumors. Results: ERBB1 and ERBB2 inhibition rapidly (within 3 h) inhibits both tumor cell motility and intravasation. Using gefitinib, ERBB1 inhibition rapidly inhibits tumor cell motility and invasion but not intravasation, whereas ERBB2 inhibition by AG825 rapidly blocks intravasation. Conclusions: ERBB1 and ERBB2 inhibition can rapidly block tumor cell invasive properties. In addition, we differentiate for the first time the contributions of ERBB1 and ERBB2 to the key metastatic properties of in vivo tumor cell invasion and intravasation. These experiments temporally and molecularly separate two key stages in tumor cell entry into blood vessels: invasion and intravasation. These results indicate that ERBB inhibition should be considered for blocking other tumor cell malignant properties besides growth.

UR - http://www.scopus.com/inward/record.url?scp=66649126942&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66649126942&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-08-2163

DO - 10.1158/1078-0432.CCR-08-2163

M3 - Article

VL - 15

SP - 3733

EP - 3739

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 11

ER -