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Eukaryotic expression cloning with an antimetastatic monoclonal antibody identifies a tetraspanin (peta-3/cd151) as an effector of human tumor cell migration and metastasis

Academic Article
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Overview

authors

  • Testa, J. E.
  • Brooks, P. C.
  • Lin, J. M.
  • Quigley, James

publication date

  • August 1999

journal

  • Cancer Research  Journal

abstract

  • A monoclonal antibody (mAb), 50-6, generated by subtractive immunization, was found to specifically inhibit in vivo metastasis of a human epidermoid carcinoma cell line, HEp-3. The cDNA of the cognate antigen of mAb 50-6 was isolated by a modified eukaryotic expression cloning protocol from a HEp-3 library. Sequence analysis identified the antigen as PETA-3/CD151, a recently described member of the tetraspanin family of proteins. The cloned antigen was also recognized by a previously described antimetastatic antibody, mAb 1A5. Inhibition of HEp-3 metastasis by the mAbs could not be attributed to any effect of the antibodies on tumor cell growth in vitro or in vivo. Rather, the antibodies appeared to inhibit an early step in the formation of metastatic foci. In a chemotaxis assay, HEp-3 migration was blocked by both antibodies. HeLa cells transfected with and overexpressing PETA-3/CD151 were more migratory than control transfectants expressing little CD151. The increase in HeLa migration was inhibitable by both mAb 50-6 and mAb 1A5. PETA-3 appears not to be involved in cell attachment because adhesion did not correlate with levels of PETA-3 expression and was unaffected by mAb 50-6 or mAb 1A5. The ability of PETA-3 to mediate cell migration suggests a mechanism by which this protein may influence metastasis. These data identify PETA-3/CD151 as the first member of the tetraspanin family to be linked as a positive effector of metastasis.

subject areas

  • Adenocarcinoma
  • Animals
  • Antibodies, Monoclonal
  • Antibodies, Neoplasm
  • Antigens, CD
  • Antigens, CD151
  • Breast Neoplasms
  • COS Cells
  • Carcinoma, Squamous Cell
  • Cell Adhesion
  • Cell Movement
  • Cercopithecus aethiops
  • Chick Embryo
  • Cloning, Molecular
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fibrosarcoma
  • HeLa Cells
  • Humans
  • Molecular Weight
  • Neoplasm Metastasis
  • Transfection
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Identity

International Standard Serial Number (ISSN)

  • 0008-5472

PubMed ID

  • 10447000
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Additional Document Info

start page

  • 3812

end page

  • 3820

volume

  • 59

issue

  • 15

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