Induction of experimental bone metastasis in mice by transfection of integrin alpha 4 beta 1 into tumor cells.
Cell adhesion receptors (eg, integrins and CD44) play an important role in invasion and metastasis during tumor progression. The increase in integrin alpha 4 beta 1 expression on primary melanomas has been reported to significantly correlate with the development of metastases. alpha 4 beta 1 is a cell surface heterodimer that mediates cell-cell and cell-extracellular matrix interactions through adhesion to vascular cell adhesion molecule (VCAM)-1 and to the IIICS region of fibronectin. To test the effects of alpha 4 beta 1 expression on tumor cell metastasis, Chinese hamster ovary cells were transfected with human alpha 4 cDNA. Whereas alpha 4-negative Chinese hamster ovary cells developed only 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 antibody against alpha 4 or VCAM-1. Expression of alpha 3 beta 1, alpha 6 beta 1, or alpha V beta 1 did not induce bone metastasis. Expression of alpha 4 beta 1 also induced bone metastasis in K562 human erythroleukemia cells injected into SCID mice. These results demonstrate that alpha 4 beta 1 can induce tumor cell trafficking to bone, probably via interaction with VCAM-1 that is constitutively expressed on bone marrow stromal cells.
Matsuura
N
N
Department of Pathology II, Wakayama Medical School, Japan.
Puzon-McLaughlin
W
W
Irie
A
A
Morikawa
Y
Y
Kakudo
K
K
Takada
Y
Y
D000818:Animals; D001859:Bone Neoplasms / Q000556:secondary*; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000473:pathology*; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*
D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing