title: Functional suppression of integrin beta 4-mediated adhesion caused by in vivo sequential selection for cancer cell intravasation.
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.
authors: Department of Pathology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan. takahide@kanazawa-med.ac.jp
authors: T
authors: T
authors: Ota
authors: M
authors: M
authors: Maeda
authors: M
authors: M
authors: Tanino
authors: M
authors: M
authors: Tatsuka
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000473:pathology*; D002448:Cell Adhesion; D005109:Extracellular Matrix / Q000378:metabolism; D039663:Integrin beta4; D007797:Laminin / Q000378:metabolism; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis
chemical_list: D015703:Antigens, CD; D039663:Integrin beta4; D007797:Laminin