N. Matsuura et al., INDUCTION OF EXPERIMENTAL BONE METASTASIS IN MICE BY TRANSFECTION OF INTEGRIN ALPHA-4-BETA-1 INTO TUMOR-CELLS, The American journal of pathology, 148(1), 1996, pp. 55-61
Cell adhesion receptors (eg, integrins and CD44) play an important rol
e in invasion and metastasis during tumor progression. The increase in
integrin alpha 4 beta 1 expression on primary melanomas has been repo
rted to significantly correlate with the development of metastases. al
pha 4 beta 1 is a cell surface heterodimer that mediates cell-cell and
cell-extracellular matrix interactions through adhesion to vascular c
ell adhesion molecule (VCAM)-1 and to the IIICS region of fibronectin.
To test the effects of alpha 4 beta 1 expression on tumor cell metast
asis, Chinese hamster ovary cells were transfected with human alpha 4
cDNA. Whereas alpha 4-negative Chinese hamster ovary cells developed o
nly pulmonary metastasis, alpha 4-positive Chinese hamster ovary cells
developed bone and pulmonary metastasis in 3 to 4 weeks when injected
intravenously into nude mice. Bone metastasis was inhibited by antibo
dy against alpha 4 or VCAM-1. Expression of alpha 3 beta 1, alpha 6 be
ta 1, or alpha V beta 1 did not induce bone metastasis. Expression of
alpha 4 beta 1 also induced bone metastasis in K562 human erythroleuke
mia cells injected into SCID mice. These results demonstrate that alph
a 4 beta 1 can induce tumor cell trafficking to bone, probably via int
eraction with VCAM-1 that is constitutively expressed on bone marrow s
tromal cells.