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α-Parvin, a pseudopodial constituent, promotes cell motility and is associated with lymph node metastasis of lobular breast carcinoma

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Abstract

Invasive lobular carcinoma (ILC) is more frequently lymph node positive than is invasive ductal carcinoma (IDC), and ILC cell infiltration shows distinctive histological characteristics, suggesting the action of ILC-specific invasion molecules. To identify such a molecule, we used a proteomic approach in the pseudopodia of MDA-MB-231 breast cancer cells. A pseudopodial constituent was identified using excimer laser ablation, two-dimensional difference gel electrophoresis, mass spectroscopy, and immunocytofluorescence. MDA-MB-231 cells were modified to express various levels of this constituent by transient transfection and were examined for pseudopodia formation and migratory abilities using wound healing and two-chamber assays. Immunohistochemical positivity of human breast cancer cells (56 ILCs and 21 IDCs) was compared with clinicopathological variables. An actin-binding adaptor protein, α-parvin, was found to localize to pseudopodia and to form focal adhesions in cells not induced to extend pseudopodia. Pseudopodial length and density and migratory abilities correlated with α-parvin expression. Twenty-one (37.5 %) ILCs stained positive for α-parvin, whereas the results were negative for all 21 IDCs (P < 0.001). α-Parvin positivity in ILC was significantly associated with lymphatic invasion (P = 0.038) and lymph node metastasis (P = 0.003) in univariate analyses and to lymph node metastasis (P = 0.020) in multivariate analyses. α-Parvin, a pseudopodial constituent, was found to promote migration of breast cancer cells and to be expressed exclusively by ILC, suggesting that α-parvin is an ILC-specific invasion molecule that may have clinical utility as a biomarker for aggressive subsets of ILC.

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Abbreviations

ILC:

Invasive lobular carcinoma

IDC:

Invasive ductal carcinoma

2D-DIGE:

Two-dimensional difference gel electrophoresis

LC–MS/MS:

Liquid chromatography-tandem mass spectroscopy

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Acknowledgments

The authors thank Yasumitsu Akahoshi (Kinki University) for technical assistance. This study was supported by the Japan Society for the Promotion of Science Kakenhi (24890274 and 25860302 to MH, 24659184 to TI, 24890137 to TM, 24390329 and 24659633 to MO, and 24590492 to AI), and grants from The Yasuda Medical Foundation and The Osaka Medical Research Foundation for Intractable Diseases. This work was partly carried out at the Analysis Center of Life Science, Natural Science Center for Basic Research and Development, Hiroshima University.

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None.

Ethical standards

The ethics committee of Kinki University Faculty of Medicine approved the experimental protocol (No. 22-40).

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Authors and Affiliations

  1. Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, 734-8551, Japan

    Masaoki Ito, Takahiro Mimae & Morihito Okada

  2. Department of Pathology, Faculty of Medicine, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan

    Man Hagiyama, Takao Inoue, Takashi Kato, Azusa Yoneshige & Akihiko Ito

  3. Nidek Co. Ltd., Gamagori, Aichi, 443-0038, Japan

    Jun Nakanishi

  4. Division of Pharmacoproteomics, National Cancer Center Research Institute, Tokyo, 104-0045, Japan

    Tadashi Kondo

Authors
  1. Masaoki Ito
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  2. Man Hagiyama
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  3. Takahiro Mimae
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  4. Takao Inoue
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  5. Takashi Kato
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  6. Azusa Yoneshige
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  7. Jun Nakanishi
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  8. Tadashi Kondo
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  9. Morihito Okada
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  10. Akihiko Ito
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Corresponding author

Correspondence to Akihiko Ito.

Additional information

Masaoki Ito and Man Hagiyama have contributed equally to this work.

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Ito, M., Hagiyama, M., Mimae, T. et al. α-Parvin, a pseudopodial constituent, promotes cell motility and is associated with lymph node metastasis of lobular breast carcinoma. Breast Cancer Res Treat 144, 59–69 (2014). https://doi.org/10.1007/s10549-014-2859-0

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  • DOI: https://doi.org/10.1007/s10549-014-2859-0

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