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

Masaoki Ito, Man Hagiyama, Takahiro Mimae, Takao Inoue, Takashi Kato, Azusa Yoneshige, Jun Nakanishi, Tadashi Kondo, Morihito Okada, Akihiko Ito

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)59-69
Number of pages11
JournalBreast Cancer Research and Treatment
Volume144
Issue number1
DOIs
Publication statusPublished - 2014 Feb
Externally publishedYes

Keywords

  • Adaptor protein
  • Biomarker
  • Excimer laser ablation
  • Invasive ductal carcinoma
  • Lymphatic invasion

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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