Tumour-associated macrophages correlate with poor prognosis in myxoid liposarcoma and promote cell motility and invasion via the HB-EGF-EGFR-PI3K/Akt pathways

A. Nabeshima, Y. Matsumoto, J. Fukushi, K. Iura, T. Matsunobu, M. Endo, T. Fujiwara, K. Iida, Y. Fujiwara, M. Hatano, N. Yokoyama, S. Fukushima, Y. Oda, Y. Iwamoto

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Abstract

Background:Myxoid liposarcoma (MLS) is the second most common subtype of liposarcoma, and metastasis occurs in up to one-third of cases. However, the mechanisms of invasion and metastasis remain unclear. Tumour-associated macrophages (TAMs) have important roles in tumour invasion, metastasis, and/or poor prognosis. The aim of this study was to investigate the relationship between TAMs and MLS.Methods:Using 78 primary MLS samples, the association between clinical prognosis and macrophage infiltration was evaluated by immunochemistry. The effects of macrophages on cell growth, cell motility, and invasion of MLS cell lines were investigated in vitro. In addition, clinicopathological factors were analysed to assess their prognostic implications in MLS.Results:Higher levels of CD68-positive macrophages were associated with poorer overall survival in MLS samples. Macrophage-conditioned medium enhanced MLS cell motility and invasion by activating epidermal growth factor receptor (EGFR), with the key ligand suggested to be heparin-binding EGF-like growth factor (HB-EGF). The phosphoinositide 3-kinase/Akt pathway was mostly involved in HB-EGF-induced cell motility and invasion of MLS. The expression of phosphorylated EGFR in MLS clinical samples was associated with macrophage infiltration. In addition, more significant macrophage infiltration was associated with poor prognosis even in multivariate analysis.Conclusions:Macrophage infiltration in MLS predicts poor prognosis, and the relationship between TAMs and MLS may be a new candidate for therapeutic targets of MLS.

Original languageEnglish
Pages (from-to)547-555
Number of pages9
JournalBritish journal of cancer
Volume112
Issue number3
DOIs
Publication statusPublished - Feb 3 2015

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Myxoid Liposarcoma
Phosphatidylinositol 3-Kinases
Epidermal Growth Factor Receptor
Cell Movement
Macrophages
Neoplasms
Neoplasm Metastasis
Heparin-binding EGF-like Growth Factor
Immunochemistry
Liposarcoma
1-Phosphatidylinositol 4-Kinase
Conditioned Culture Medium

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Tumour-associated macrophages correlate with poor prognosis in myxoid liposarcoma and promote cell motility and invasion via the HB-EGF-EGFR-PI3K/Akt pathways. / Nabeshima, A.; Matsumoto, Y.; Fukushi, J.; Iura, K.; Matsunobu, T.; Endo, M.; Fujiwara, T.; Iida, K.; Fujiwara, Y.; Hatano, M.; Yokoyama, N.; Fukushima, S.; Oda, Y.; Iwamoto, Y.

In: British journal of cancer, Vol. 112, No. 3, 03.02.2015, p. 547-555.

Research output: Contribution to journalArticle

Nabeshima, A. ; Matsumoto, Y. ; Fukushi, J. ; Iura, K. ; Matsunobu, T. ; Endo, M. ; Fujiwara, T. ; Iida, K. ; Fujiwara, Y. ; Hatano, M. ; Yokoyama, N. ; Fukushima, S. ; Oda, Y. ; Iwamoto, Y. / Tumour-associated macrophages correlate with poor prognosis in myxoid liposarcoma and promote cell motility and invasion via the HB-EGF-EGFR-PI3K/Akt pathways. In: British journal of cancer. 2015 ; Vol. 112, No. 3. pp. 547-555.
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abstract = "Background:Myxoid liposarcoma (MLS) is the second most common subtype of liposarcoma, and metastasis occurs in up to one-third of cases. However, the mechanisms of invasion and metastasis remain unclear. Tumour-associated macrophages (TAMs) have important roles in tumour invasion, metastasis, and/or poor prognosis. The aim of this study was to investigate the relationship between TAMs and MLS.Methods:Using 78 primary MLS samples, the association between clinical prognosis and macrophage infiltration was evaluated by immunochemistry. The effects of macrophages on cell growth, cell motility, and invasion of MLS cell lines were investigated in vitro. In addition, clinicopathological factors were analysed to assess their prognostic implications in MLS.Results:Higher levels of CD68-positive macrophages were associated with poorer overall survival in MLS samples. Macrophage-conditioned medium enhanced MLS cell motility and invasion by activating epidermal growth factor receptor (EGFR), with the key ligand suggested to be heparin-binding EGF-like growth factor (HB-EGF). The phosphoinositide 3-kinase/Akt pathway was mostly involved in HB-EGF-induced cell motility and invasion of MLS. The expression of phosphorylated EGFR in MLS clinical samples was associated with macrophage infiltration. In addition, more significant macrophage infiltration was associated with poor prognosis even in multivariate analysis.Conclusions:Macrophage infiltration in MLS predicts poor prognosis, and the relationship between TAMs and MLS may be a new candidate for therapeutic targets of MLS.",
author = "A. Nabeshima and Y. Matsumoto and J. Fukushi and K. Iura and T. Matsunobu and M. Endo and T. Fujiwara and K. Iida and Y. Fujiwara and M. Hatano and N. Yokoyama and S. Fukushima and Y. Oda and Y. Iwamoto",
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T1 - Tumour-associated macrophages correlate with poor prognosis in myxoid liposarcoma and promote cell motility and invasion via the HB-EGF-EGFR-PI3K/Akt pathways

AU - Nabeshima, A.

AU - Matsumoto, Y.

AU - Fukushi, J.

AU - Iura, K.

AU - Matsunobu, T.

AU - Endo, M.

AU - Fujiwara, T.

AU - Iida, K.

AU - Fujiwara, Y.

AU - Hatano, M.

AU - Yokoyama, N.

AU - Fukushima, S.

AU - Oda, Y.

AU - Iwamoto, Y.

PY - 2015/2/3

Y1 - 2015/2/3

N2 - Background:Myxoid liposarcoma (MLS) is the second most common subtype of liposarcoma, and metastasis occurs in up to one-third of cases. However, the mechanisms of invasion and metastasis remain unclear. Tumour-associated macrophages (TAMs) have important roles in tumour invasion, metastasis, and/or poor prognosis. The aim of this study was to investigate the relationship between TAMs and MLS.Methods:Using 78 primary MLS samples, the association between clinical prognosis and macrophage infiltration was evaluated by immunochemistry. The effects of macrophages on cell growth, cell motility, and invasion of MLS cell lines were investigated in vitro. In addition, clinicopathological factors were analysed to assess their prognostic implications in MLS.Results:Higher levels of CD68-positive macrophages were associated with poorer overall survival in MLS samples. Macrophage-conditioned medium enhanced MLS cell motility and invasion by activating epidermal growth factor receptor (EGFR), with the key ligand suggested to be heparin-binding EGF-like growth factor (HB-EGF). The phosphoinositide 3-kinase/Akt pathway was mostly involved in HB-EGF-induced cell motility and invasion of MLS. The expression of phosphorylated EGFR in MLS clinical samples was associated with macrophage infiltration. In addition, more significant macrophage infiltration was associated with poor prognosis even in multivariate analysis.Conclusions:Macrophage infiltration in MLS predicts poor prognosis, and the relationship between TAMs and MLS may be a new candidate for therapeutic targets of MLS.

AB - Background:Myxoid liposarcoma (MLS) is the second most common subtype of liposarcoma, and metastasis occurs in up to one-third of cases. However, the mechanisms of invasion and metastasis remain unclear. Tumour-associated macrophages (TAMs) have important roles in tumour invasion, metastasis, and/or poor prognosis. The aim of this study was to investigate the relationship between TAMs and MLS.Methods:Using 78 primary MLS samples, the association between clinical prognosis and macrophage infiltration was evaluated by immunochemistry. The effects of macrophages on cell growth, cell motility, and invasion of MLS cell lines were investigated in vitro. In addition, clinicopathological factors were analysed to assess their prognostic implications in MLS.Results:Higher levels of CD68-positive macrophages were associated with poorer overall survival in MLS samples. Macrophage-conditioned medium enhanced MLS cell motility and invasion by activating epidermal growth factor receptor (EGFR), with the key ligand suggested to be heparin-binding EGF-like growth factor (HB-EGF). The phosphoinositide 3-kinase/Akt pathway was mostly involved in HB-EGF-induced cell motility and invasion of MLS. The expression of phosphorylated EGFR in MLS clinical samples was associated with macrophage infiltration. In addition, more significant macrophage infiltration was associated with poor prognosis even in multivariate analysis.Conclusions:Macrophage infiltration in MLS predicts poor prognosis, and the relationship between TAMs and MLS may be a new candidate for therapeutic targets of MLS.

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