The EGF/CSF-1 Paracrine Invasion Loop Can Be Triggered by Heregulin beta 1 and CXCL12

L. Hernandez, T. Smirnova, D. Kedrin, J. Wyckoff, L. Zhu, E.R. Stanley, D.G. Cox, W.J. Muller, J.W. Pollard, N. van Rooijen, J.E. Segall

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

An important step in the process of metastasis from the primary tumor is invasive spread into the surrounding stroma. Using an in vivo invasion assay, we have previously shown that imposed gradients of epidermal growth factor (EGF) or colony-stimulating factor-1 (CSF-1) can induce invasion through an EGF/CSF-1 paracrine loop between cancer cells and macrophages. We now report that invasion induced by other ligands also relies on this EGF/CSF-1 paracrine invasive loop. Using an in vivo invasion assay, we show that MTLn3 breast cancer cells overexpressing ErbB3 exhibit enhanced invasion compared with control MTLn3 cells in response to the ErbB3 ligand HRG-beta 1. The invasive response of both MTLn3-ErbB3 and transgenic MMTV-Neu tumors to HRG-beta 1 is inhibited by blocking EGF receptor, CSF-1 receptor, or macrophage function, indicating that invasiveness to HRG-beta 1 is dependent on the EGF/CSF-1 paracrine loop. Furthermore, we show that CXCL12 also triggers in vivo invasion of transgenic MMTV-PyMT tumors in an EGF/CSF-1-dependent manner. Although the invasion induced by HRG-beta 1 or CXCL12 is dependent on the EGF/CSF-1 paracrine loop, invasion induced by EGF is not dependent on HRG-beta 1 or CXCL12 signaling, showing an asymmetrical relationship between different ligand/receptor systems in driving invasion. Our results identify a stromal/tumor interaction that acts as an engine underlying invasion induced by multiple ligands. [Cancer lies 2009;69(7):3221-7]
Original languageUndefined/Unknown
Pages (from-to)3221-3227
JournalCancer Research
Volume69
Issue number7
DOIs
Publication statusPublished - 2009

Cite this

Hernandez, L., Smirnova, T., Kedrin, D., Wyckoff, J., Zhu, L., Stanley, E. R., ... Segall, J. E. (2009). The EGF/CSF-1 Paracrine Invasion Loop Can Be Triggered by Heregulin beta 1 and CXCL12. Cancer Research, 69(7), 3221-3227. https://doi.org/10.1158/0008-5472.CAN-08-2871
Hernandez, L. ; Smirnova, T. ; Kedrin, D. ; Wyckoff, J. ; Zhu, L. ; Stanley, E.R. ; Cox, D.G. ; Muller, W.J. ; Pollard, J.W. ; van Rooijen, N. ; Segall, J.E. / The EGF/CSF-1 Paracrine Invasion Loop Can Be Triggered by Heregulin beta 1 and CXCL12. In: Cancer Research. 2009 ; Vol. 69, No. 7. pp. 3221-3227.
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title = "The EGF/CSF-1 Paracrine Invasion Loop Can Be Triggered by Heregulin beta 1 and CXCL12",
abstract = "An important step in the process of metastasis from the primary tumor is invasive spread into the surrounding stroma. Using an in vivo invasion assay, we have previously shown that imposed gradients of epidermal growth factor (EGF) or colony-stimulating factor-1 (CSF-1) can induce invasion through an EGF/CSF-1 paracrine loop between cancer cells and macrophages. We now report that invasion induced by other ligands also relies on this EGF/CSF-1 paracrine invasive loop. Using an in vivo invasion assay, we show that MTLn3 breast cancer cells overexpressing ErbB3 exhibit enhanced invasion compared with control MTLn3 cells in response to the ErbB3 ligand HRG-beta 1. The invasive response of both MTLn3-ErbB3 and transgenic MMTV-Neu tumors to HRG-beta 1 is inhibited by blocking EGF receptor, CSF-1 receptor, or macrophage function, indicating that invasiveness to HRG-beta 1 is dependent on the EGF/CSF-1 paracrine loop. Furthermore, we show that CXCL12 also triggers in vivo invasion of transgenic MMTV-PyMT tumors in an EGF/CSF-1-dependent manner. Although the invasion induced by HRG-beta 1 or CXCL12 is dependent on the EGF/CSF-1 paracrine loop, invasion induced by EGF is not dependent on HRG-beta 1 or CXCL12 signaling, showing an asymmetrical relationship between different ligand/receptor systems in driving invasion. Our results identify a stromal/tumor interaction that acts as an engine underlying invasion induced by multiple ligands. [Cancer lies 2009;69(7):3221-7]",
author = "L. Hernandez and T. Smirnova and D. Kedrin and J. Wyckoff and L. Zhu and E.R. Stanley and D.G. Cox and W.J. Muller and J.W. Pollard and {van Rooijen}, N. and J.E. Segall",
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Hernandez, L, Smirnova, T, Kedrin, D, Wyckoff, J, Zhu, L, Stanley, ER, Cox, DG, Muller, WJ, Pollard, JW, van Rooijen, N & Segall, JE 2009, 'The EGF/CSF-1 Paracrine Invasion Loop Can Be Triggered by Heregulin beta 1 and CXCL12' Cancer Research, vol. 69, no. 7, pp. 3221-3227. https://doi.org/10.1158/0008-5472.CAN-08-2871

The EGF/CSF-1 Paracrine Invasion Loop Can Be Triggered by Heregulin beta 1 and CXCL12. / Hernandez, L.; Smirnova, T.; Kedrin, D.; Wyckoff, J.; Zhu, L.; Stanley, E.R.; Cox, D.G.; Muller, W.J.; Pollard, J.W.; van Rooijen, N.; Segall, J.E.

In: Cancer Research, Vol. 69, No. 7, 2009, p. 3221-3227.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The EGF/CSF-1 Paracrine Invasion Loop Can Be Triggered by Heregulin beta 1 and CXCL12

AU - Hernandez, L.

AU - Smirnova, T.

AU - Kedrin, D.

AU - Wyckoff, J.

AU - Zhu, L.

AU - Stanley, E.R.

AU - Cox, D.G.

AU - Muller, W.J.

AU - Pollard, J.W.

AU - van Rooijen, N.

AU - Segall, J.E.

PY - 2009

Y1 - 2009

N2 - An important step in the process of metastasis from the primary tumor is invasive spread into the surrounding stroma. Using an in vivo invasion assay, we have previously shown that imposed gradients of epidermal growth factor (EGF) or colony-stimulating factor-1 (CSF-1) can induce invasion through an EGF/CSF-1 paracrine loop between cancer cells and macrophages. We now report that invasion induced by other ligands also relies on this EGF/CSF-1 paracrine invasive loop. Using an in vivo invasion assay, we show that MTLn3 breast cancer cells overexpressing ErbB3 exhibit enhanced invasion compared with control MTLn3 cells in response to the ErbB3 ligand HRG-beta 1. The invasive response of both MTLn3-ErbB3 and transgenic MMTV-Neu tumors to HRG-beta 1 is inhibited by blocking EGF receptor, CSF-1 receptor, or macrophage function, indicating that invasiveness to HRG-beta 1 is dependent on the EGF/CSF-1 paracrine loop. Furthermore, we show that CXCL12 also triggers in vivo invasion of transgenic MMTV-PyMT tumors in an EGF/CSF-1-dependent manner. Although the invasion induced by HRG-beta 1 or CXCL12 is dependent on the EGF/CSF-1 paracrine loop, invasion induced by EGF is not dependent on HRG-beta 1 or CXCL12 signaling, showing an asymmetrical relationship between different ligand/receptor systems in driving invasion. Our results identify a stromal/tumor interaction that acts as an engine underlying invasion induced by multiple ligands. [Cancer lies 2009;69(7):3221-7]

AB - An important step in the process of metastasis from the primary tumor is invasive spread into the surrounding stroma. Using an in vivo invasion assay, we have previously shown that imposed gradients of epidermal growth factor (EGF) or colony-stimulating factor-1 (CSF-1) can induce invasion through an EGF/CSF-1 paracrine loop between cancer cells and macrophages. We now report that invasion induced by other ligands also relies on this EGF/CSF-1 paracrine invasive loop. Using an in vivo invasion assay, we show that MTLn3 breast cancer cells overexpressing ErbB3 exhibit enhanced invasion compared with control MTLn3 cells in response to the ErbB3 ligand HRG-beta 1. The invasive response of both MTLn3-ErbB3 and transgenic MMTV-Neu tumors to HRG-beta 1 is inhibited by blocking EGF receptor, CSF-1 receptor, or macrophage function, indicating that invasiveness to HRG-beta 1 is dependent on the EGF/CSF-1 paracrine loop. Furthermore, we show that CXCL12 also triggers in vivo invasion of transgenic MMTV-PyMT tumors in an EGF/CSF-1-dependent manner. Although the invasion induced by HRG-beta 1 or CXCL12 is dependent on the EGF/CSF-1 paracrine loop, invasion induced by EGF is not dependent on HRG-beta 1 or CXCL12 signaling, showing an asymmetrical relationship between different ligand/receptor systems in driving invasion. Our results identify a stromal/tumor interaction that acts as an engine underlying invasion induced by multiple ligands. [Cancer lies 2009;69(7):3221-7]

U2 - 10.1158/0008-5472.CAN-08-2871

DO - 10.1158/0008-5472.CAN-08-2871

M3 - Article

VL - 69

SP - 3221

EP - 3227

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 7

ER -

Hernandez L, Smirnova T, Kedrin D, Wyckoff J, Zhu L, Stanley ER et al. The EGF/CSF-1 Paracrine Invasion Loop Can Be Triggered by Heregulin beta 1 and CXCL12. Cancer Research. 2009;69(7):3221-3227. https://doi.org/10.1158/0008-5472.CAN-08-2871