Suppression of ruffling by the EGF receptor in chemotactic cells

Jeffrey B. Wyckoff, Lauren Insel, Khashayarsha Khazaie, Rosemarie B. Lichtner, John S. Condeelis, Jeffrey E. Segall

Research output: Contribution to journalArticle

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Abstract

To clarify the relationship between ruffling and lamellipod extension in growth factor-stimulated chemotactic responses, we utilized cell lines derived from the rat 13762 NF mammary adenocarcinoma. Non-metastatic MTC cells expressing the human EGF receptor (termed MTC HER cells) demonstrated chemotactic responses to TGF-α, an EGF receptor ligand typically present in mammary tissue. In microchemotaxis chambers, peak chemotactic responses occurred in response to 5 nM TGF-α. MTC HER cells showed dramatic ruffling edges in the absence of external stimuli, and addition of 5 nM TGF-α led to a transient reduction in ruffling concomitant with lamellipod extension. Lamellipod extension correlated with an overall increase in actin polymerization. These responses were blocked by the PI 3 kinase inhibitor wortmannin but not by the MAP kinase inhibitors PD98059 and SB203580. We conclude that the initial chemotactic response to TGF-α involves lamellipod extension and that ruffling reflects a dynamic turnover of lamellipodia that is arrested during lamellipod extension. By regulating the dissolution of ruffles and extension of lamellipods, a chemotactic response can be achieved, which may contribute to the metastatic process.

Original languageEnglish (US)
Pages (from-to)100-109
Number of pages10
JournalExperimental Cell Research
Volume242
Issue number1
DOIs
StatePublished - Jul 10 1998

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Epidermal Growth Factor Receptor
Breast
Pseudopodia
Phosphatidylinositol 3-Kinases
Polymerization
Actins
Intercellular Signaling Peptides and Proteins
Adenocarcinoma
Phosphotransferases
Cell Line

ASJC Scopus subject areas

  • Cell Biology

Cite this

Suppression of ruffling by the EGF receptor in chemotactic cells. / Wyckoff, Jeffrey B.; Insel, Lauren; Khazaie, Khashayarsha; Lichtner, Rosemarie B.; Condeelis, John S.; Segall, Jeffrey E.

In: Experimental Cell Research, Vol. 242, No. 1, 10.07.1998, p. 100-109.

Research output: Contribution to journalArticle

Wyckoff, Jeffrey B. ; Insel, Lauren ; Khazaie, Khashayarsha ; Lichtner, Rosemarie B. ; Condeelis, John S. ; Segall, Jeffrey E. / Suppression of ruffling by the EGF receptor in chemotactic cells. In: Experimental Cell Research. 1998 ; Vol. 242, No. 1. pp. 100-109.
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