Gong Lin, Zheng Ying, Liu Shanling, Peng Zhilan
Department of Obstetrics and Gynecology, West China Second Hospital, West China Center of Medical Sciences, Sichuan University,Chengdu, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children ,Sichuan University, Chengdu, China. Email:
Asian Pac J Cancer Prev. 2018 Sep 26;19(9):2493-2498. doi: 10.22034/APJCP.2018.19.9.2493.
Objective: To investigate the regulatory role of fibronectin (FN) in the formation of multicellular aggregate (MCA) in ovarian cancer SKOV3 and OVCAR-3 cells and integrin expression. Methods: The dynamic formation of MCA in SKOV3 and OVCAR-3 was determined using the liquid overlay technique in the presence or absence of FN, anti-FN, RGD peptide, control RGE. The expression of α3β1, α4β1 and α5β1 integrin in monolayer cells, MCA and FN-treated MCA were determined by flow cytometry and quantitative RT-PCR. Results: OVCAR-3 and SKOV3 MCA were formed on the 4th and 8th day and peaked on the 6th and 9th day, respectively. Treatment with different concentrations of FN, LN, type IV collagen and control RGE peptide promoted MCA growth, which was mitigated by anti-FN and RGD peptide. In comparison with monolayer cells, up-regulated α3β1, α4β1 and α5β1 expression were detected in MCA while treatment with FN in both cells. Conclusions: OVCAR-3 and SKOV3 cells had varying dynamic formation of MCA in our experimental system. FN enhanced MCA formation in both cells, which was associated with increased expression of 3β1, α4β1 and α5β1 in the MCA. Therefore, FN and these integrins may be new therapeutic targets for intervention of ovarian cancer metastasis.
研究纤连蛋白（FN）在卵巢癌SKOV3和OVCAR-3细胞中多细胞聚集体（MCA）形成及整合素表达中的调节作用。方法：采用液体覆盖技术，在有或无FN、抗FN、RGD肽、对照RGE的情况下，测定SKOV3和OVCAR-3中MCA的动态形成。通过流式细胞术和定量逆转录聚合酶链反应测定单层细胞、MCA和FN处理的MCA中α3β1、α4β1和α5β1整合素的表达。结果：OVCAR-3和SKOV3 MCA分别在第4天和第8天形成，并分别在第6天和第9天达到峰值。用不同浓度的FN、层粘连蛋白、IV型胶原和对照RGE肽处理可促进MCA生长，而抗FN和RGD肽可减轻这种生长。与单层细胞相比，在MCA中检测到α3β1、α4β1和α5β1表达上调，且两种细胞均用FN处理。结论：在我们的实验系统中，OVCAR-3和SKOV3细胞具有不同的MCA动态形成。FN增强了两种细胞中MCA的形成，这与MCA中3β1、α4β1和α5β1表达增加有关。因此，FN和这些整合素可能是干预卵巢癌转移的新治疗靶点。
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