J. Klominek et al., A TUMOR-DERIVED MOTILITY FACTOR THAT STIMULATES CELL-MIGRATION ON EXTRACELLULAR-MATRIX, Anticancer research, 18(3A), 1998, pp. 1601-1612
A factor that stimulates migration of lung carcinoma cells on biologic
al substrata was purified fi om the human lung adenocarcinoma cell lin
e WART. A partially purified autocrine motility factor-like substance,
termed haptotaxin, was added to the lower compartment of Boyden chamb
ers and the filters were coated on the upper, lower or both sides with
different concentrations of the extracellular matrix (ECM) components
fibronectin, laminin or collagen type IV. These adhesive proteins coa
ted on the lower surface of the filter promoted the migration (haptota
xis) of lung carcinoma cells. This effect was greatly enhanced by the
addition of haptotaxin. In contrast, ECM components (including gelatin
) coated on the upper surface or on both filter surfaces did not stimu
late tumor cell migration. However, the addition of haptotaxin also ti
mulated cell migration under these conditions. Haptotaxin did not stim
ulate migration on filters coated with bovine serum albumin ol on unco
ated filters. Haptotaxin could not be absorbed by fibronectin, laminin
, collagen type IV or gelatin, and soluble ECM components did not affe
ct the locomotor effect of haptotaxin. Substrata coated with fibronect
in, laminin and collagen type IV induced adhesion and spreading of lun
g carcinoma cells in a dose dependent fashion. Haptotaxin potentiated
adhesion and spreading of tumor cells on these substrata but did not i
n itself mediate adhesion and spreading of the cells. Anti-VLA 2 antib
odies inhibited migration to haptotaxin on gelatin and laminin coated
filters but did not affect haptotaxin-induced migration on fibronectin
or collagen type IV substrata. Anti-VLA5 monoclonal antibodies inhibi
ted haptotaxin-induced migration on fibronectin coated filters but not
such migration on filters coated with other ECM molecules showing tha
t tumor cells must intel act specifically with ECM components in order
to migrate to haptotaxin.