Integrin β1與Syndecan-4在子宮肌瘤細胞貼附所扮演的角色

Abstract

Uterine leiomyoma is a benign tumor that originates from myometrium in women of the reproductive age. Compared to myometrium, leiomyoma contains excessive extracellular matrix (ECM). Integrins are the major adhesion molecules on cell surface to interact with ECM. Syndecans (SDCs) are transmembrane proteoglycans that cooperate with integrins in focal adhesion formation. The interactions of ECM with integrins and syndecans regulate cell adhesion and initiate signals for cell growth, differentiation and migration. My study focused on the role of integrin β1 and syndecan-4 in leiomyomal cell adhesion. Leiomyomal cells were isolated from leiomyomal tissues obtained from patients who underwent hysterectomy. Cells were transfected with siRNA of integrin β1 or scramble control and their adhesive ability were evaluated on fibronectin- or collagen-coated wells. Integrin β1-specific siRNA suppressed integrin expression, but did not significantly reduce cell adhesion. Cell adhesion to fibronectin induced phosphorylaltion of focal adhesion knase (FAK). Integrin β1 knockdown slightly decreased phosphorylation of FAK. An RGD sequence-containing protein, which blocks the interaction of integrins with matrix, decreased cell adhesion. We found that leiomyomal cells also expressed integrin α5 and β3. To study the role of syndecan-4, we infected cells with lentivirus carrying shRNA of syndecan-4 (shSDC4). Although syndecan-4 expression was decreased by shSDC4, cell adhesion was not reduced. We further investigated the long-term effect of lacking of integrin β1. Compared with control group, cell growth rate in integrin β1-specific siRNA-treated group was reduced. All together, knockdown of integrin β1 and syndecan-4 alone did not affect cell adhesion, suggesting that redundant expression of integrin subtypes may be sufficient for cell adhesion. The role of integirn β1 in long-term regulation of cell growth remains to be investigated.