Matsuura N, Puzon-McLaughlin W, Irie A, Morikawa Y, Kakudo K, Takada Y
Department of Pathology II, Wakayama Medical School, Japan.
Am J Pathol. 1996 Jan;148(1):55-61.
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.
细胞黏附受体（如整合素和CD44）在肿瘤进展过程中的侵袭和转移中起重要作用。据报道，原发性黑色素瘤上整合素α4β1表达的增加与转移的发生显著相关。α4β1是一种细胞表面异二聚体，通过与血管细胞黏附分子（VCAM）-1和纤连蛋白的IIICS区域黏附来介导细胞-细胞和细胞-细胞外基质相互作用。为了测试α4β1表达对肿瘤细胞转移的影响，用人类α4 cDNA转染中国仓鼠卵巢细胞。α4阴性的中国仓鼠卵巢细胞仅发生肺转移，而α4阳性的中国仓鼠卵巢细胞静脉注射到裸鼠体内后，在3至4周内发生骨和肺转移。抗α4或VCAM-1抗体可抑制骨转移。α3β1、α6β1或αVβ1的表达不会诱导骨转移。α4β1的表达也可诱导注射到SCID小鼠体内的K562人红白血病细胞发生骨转移。这些结果表明，α4β1可能通过与骨髓基质细胞上组成性表达的VCAM-1相互作用，诱导肿瘤细胞向骨转移。
