title: Localization of the invadopodia-related proteins actinin-1 and cortactin to matrix-contact-side cytoplasm of cancer cells in surgically resected lung adenocarcinomas.
abstract: OBJECTIVE
  Actin-associated proteins at cell-matrix-contact sites form invadopodia in cancer cells and participate in migration, matrix degradation and invasion. We investigated an alteration of subcellular localization of invadopodia-related actin-associated proteins, actinin-1 and cortactin, in lung adenocarcinomas, its clinical significance, and its possible regulatory factors.
  
  
  METHODS
  Invadopodia-related proteins, actinin-1 and cortactin, were immunohistochemically examined in 90 cases of lung adenocarcinomas. Expression of invadopodia-associated proteins and their possible regulators in lung adenocarcinomas were examined by real-time RT-PCR, database search, and immunohistochemistry.
  
  
  RESULTS
  Actinin-1 and cortactin showed matrix-contact-side localization in adenocarcinoma cells, but rarely in normal bronchiolar epithelial cells, alveolar cells, or precursor lesion atypical adenomatous hyperplasia cells. Immunoelectron-microscopic examination of adenocarcinoma cells revealed actinin-1 localization to matrix-contact-side cytoplasm with cytoplasmic protrusions. Matrix-contact-side localization of actinin-1 and cortactin was correlated with tumor stages, lymph node metastasis, vascular permeation, and loss of basement membrane. The tumor-specific survival rate was worse for the group in which matrix-contact-side localization of cortactin was high than for the low group. mRNA of the Rho guanine exchange factor epithelial cell transforming sequence-2 (Ect2) tended to be overexpressed in lung adenocarcinomas and cytoplasmic expression of Ect2 tended to be correlated with matrix-contact-side localization of actinin-1.
  
  
  CONCLUSIONS
  Matrix-contact-side localization of invadopodia-related proteins in the lung adenocarcinoma cells were correlated with invasion, metastasis, and poor prognosis. Ect2 was a possible regulator of matrix-contact-side localization of invadopodia-related proteins.
authors.affiliation: Department of Pathology, Tokyo Medical and Dental University, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirooka
authors.forename: Takumi
authors.initials: T
authors.lastname: Akashi
authors.forename: Noboru
authors.initials: N
authors.lastname: Ando
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Noriko
authors.initials: N
authors.lastname: Ishida
authors.forename: Morito
authors.initials: M
authors.lastname: Kurata
authors.forename: Touichirou
authors.initials: T
authors.lastname: Takizawa
authors.forename: Kou
authors.initials: K
authors.lastname: Kayamori
authors.forename: Kei
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Fujiwara
authors.forename: Masao
authors.initials: M
authors.lastname: Kojima
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Eishi
mesh_terms: D000185:Actinin / Q000378:metabolism*; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018255:Adenomatosis, Pulmonary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D051356:Cortactin / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011013:Pneumonectomy; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015996:Survival Rate
chemical_list: C526905:ACTN1 protein, human; D014408:Biomarkers, Tumor; C495868:CTTN protein, human; D051356:Cortactin; C489850:ECT2 protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D000185:Actinin