Functional suppression of integrin beta 4-mediated adhesion caused by in vivo sequential selection for cancer cell intravasation

Anticancer Res. 2001 Jan-Feb;21(1A):205-11.

Abstract

Intravasation is essential for hematogenous metastasis in cancer cells, but its cellular determinants have not been well elucidated because of a lack of suitable experimental cell systems. Int-3LL was originally developed by in vivo sequential selection for intravasation from Lewis lung carcinoma (3LL) cells. Here, we found that these variant cells showed a highly penetrating ability in vitro as well as an augmented intravasating potential in vivo. In three-dimensional collagen-gel, Int-3LL cells formed diffusive colonies with less plating efficiency than their parental cells. Despite these properties, Int-3LL cells showed an ability of invasive migration in vitro similar to parental cells. On the other hand, a reduced adhesiveness and less spreading on extracellular matrices were revealed in Int-3LL cells. Analyses using anti-integrin antibodies indicated that the dysadhesion phenotype in Int-3LL cells was associated with integrin beta 4 dysfunction, which is known to produce epithelial detachment. Also, the types and the levels of integrins were not indistinguishable between Int-3LL and parental 3LL cells. Thus, the impaired function of integrin beta 4-mediated adhesion is considered to be an important factor in intravasation during metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / physiology*
  • Carcinoma, Lewis Lung / blood supply
  • Carcinoma, Lewis Lung / pathology*
  • Cell Adhesion*
  • Extracellular Matrix / metabolism
  • Integrin beta4
  • Laminin / metabolism
  • Mice
  • Neoplasm Invasiveness
  • Neoplasm Metastasis

Substances

  • Antigens, CD
  • Integrin beta4
  • Laminin