l-type amino acid transporter 1 and CD98 expression in primary and metastatic sites of human neoplasms

Cancer Sci. 2008 Dec;99(12):2380-6. doi: 10.1111/j.1349-7006.2008.00969.x. Epub 2008 Nov 17.


The significance of L-type amino acid transporter (LAT) 1 expression remains unclear in the metastatic process of human neoplasms, whereas experimental studies have demonstrated that LAT1 is associated with the metastatic process of cancer cells. We compared the immunohistochemical expression of LAT1 and CD98 between the primary site and a concordant pulmonary metastatic site in 93 cancer patients, all of whom had undergone thoracotomy. LAT1, CD98, Ki-67 labeling index, vascular endothelial growth factor (VEGF), CD31, and CD34 were analyzed by immunohistochemical staining in the resected tumors of 93 cancer patients: 45 colon cancers; nine breast cancers; eight head and neck cancers; 11 genital cancers; 14 soft-tissue sarcomas; and six other cancers. The expression of these markers was significantly higher in the metastatic sites than in the primary sites. In total, the positive rates of LAT1, CD98, Ki-67, VEGF, CD31, and CD34 were 40, 24, 56, 41, 45, and 39%, respectively, in the primary sites and 65, 45, 84, 67, 73, and 61%, respectively, in the metastatic sites. LAT1 expression was closely correlated with CD98 expression, angiogenesis, and cell proliferation. The association between LAT1 and CD98 expression was strongest in the primary and metastatic sites. The present study suggests that overexpression of LAT1 and CD98 has an important role to play in the metastatic process of variable human neoplasms. Moreover, LAT1 expression was significantly correlated with cell proliferation and angiogenesis.

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD34 / metabolism
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Child
  • Female
  • Fusion Regulatory Protein-1 / metabolism*
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Large Neutral Amino Acid-Transporter 1 / metabolism*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasms / pathology*
  • Neovascularization, Pathologic
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Retrospective Studies
  • Sarcoma / metabolism
  • Sarcoma / pathology
  • Vascular Endothelial Growth Factor A / metabolism
  • Young Adult


  • Antigens, CD34
  • Fusion Regulatory Protein-1
  • Ki-67 Antigen
  • Large Neutral Amino Acid-Transporter 1
  • Platelet Endothelial Cell Adhesion Molecule-1
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A