ITGA5 inhibition in pancreatic stellate cells re-educates the in vitro tumor-stromal crosstalk
ITGA5 inhibition in pancreatic stellate cells re-educates the in vitro tumor-stromal crosstalk
复制标题
胰腺星状细胞中的 ITGA5 抑制重新教育体外肿瘤基质串扰
DOI：
10.1007/s12032-022-01902-w
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发表时间：
2022-12-05
期刊：
影响因子：
3.4
通讯作者：
Zhang，Lu
中科院分区：
文献类型：
--
作者：
Wang，Tao;Yang，Jian;Zhang，Lu
胰腺癌细胞(PCCs)和胰腺星状细胞(PSCs)之间的相互作用促进了胰腺癌的侵袭性进展，阻断肿瘤-间质串扰是一种有前途的治疗策略。整合素α5在胰腺癌间质和活化的PSCs中高表达。ITGA5在PCCs-PSCs相互作用中起中介作用，但其在调控PSCs和PCCs生物学行为中的作用尚不十分清楚。在本研究中，PSCs中的ITGA5被其特异性抑制物AV3多肽或siRNA敲除技术所抑制。用胰腺癌SW1990细胞条件培养液(SW1990-CM)和间接共培养系统模拟体外肿瘤-间质串扰的环境。结果表明，抑制ITGA5抑制PSCs的增殖和迁移，但促进自噬。SW1990细胞与PSCs共培养后，获得了肿瘤干细胞样的特性，如增加了耐药性、迁移和侵袭能力，但ITGA5基因敲除的PSCs不能产生这些作用。提示ITGA5参与了PSCs和PCCs恶性生物学行为的发生，抑制PSCs中ITGA5的表达可能通过重新调节PCCs-PSCs间的相互作用，从而有利于胰腺癌的治疗。
The interaction between pancreatic cancer cells (PCCs) and pancreatic stellate cells (PSCs) promotes aggressive progression of pancreatic cancer, and disrupting the tumor-stromal crosstalk is a promising therapeutic strategy. Integrin α5 (ITGA5) is specifically overexpressed in pancreatic cancer stroma and activated PSCs. ITGA5 acts as a mediator in PCCs-PSCs interaction, but its role in regulating biological behaviors of PSCs and PCCs is still not quite clear. In this study, ITGA5 in PSCs was inhibited using its specific inhibitor AV3 peptide or siRNA knockdown technique. Pancreatic cancer SW1990 cells conditioned medium (SW1990-CM) and an indirect co-culture system were used to mimic the environment of the in vitro tumor-stromal crosstalk. Our results showed that ITGA5 inhibition impaired the proliferation and migration of PSCs, but enhanced autophagy. After co-culture with PSCs, SW1990 cells gained some cancer stem cells (CSCs)-like characteristics, such as increased drug resistance, migration and invasion ability, but PSCs with ITGA5 knockdown were incapable of producing these effects. The present results suggested that ITGA5 was involved in the development of the malignant biological behaviors of PSCs and PCCs, and ITGA5 inhibition in PSCs might benefit the treatment of pancreatic cancer by re-educating PCCs-PSCs interaction.