TIMP-2 secreted by monocyte-like cells is a potent suppressor of invadopodia formation in pancreatic cancer cells
TIMP-2 secreted by monocyte-like cells is a potent suppressor of invadopodia formation in pancreatic cancer cells
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DOI：
10.1186/s12885-019-6429-z
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发表时间：
2019-12-13
期刊：
影响因子：
3.8
通讯作者：
Wells, Claire M.
中科院分区：
文献类型：
--
作者：
Benzing, Christian;Lam, Hoyin;Wells, Claire M.
背景：单核细胞是胰腺导管腺癌（PDAC）肿瘤微环境（TME）的主要成分。然而，肿瘤细胞和单核细胞之间复杂的相互作用及其在肿瘤侵袭中的作用尚未完全建立。方法：为了特异性地测试相互作用对侵袭潜力的影响，选择两种PDAC细胞系PaTu 8902和CFPAC-1，以确定它们形成侵袭性粘附的能力，也称为侵袭伪足和在球体侵袭测定中侵袭。有趣的是，当PDAC细胞与未分化的THP 1单核细胞样细胞共培养时，侵袭伪足的形成被显著抑制。此外，THP 1细胞的条件培养基（CM）也能够抑制侵袭伪足的形成。进一步的研究表明，在CM中存在金属蛋白酶组织抑制剂（TIMP）1和2。然而，抑制invadopodia的形成被发现是特定的TIMP 2 activity.Conclusions：我们的研究结果表明，TIMP 2水平在肿瘤微环境中可能有预后价值的PDAC患者。此外，在原发性肿瘤中激活表达TIMP 2的单核细胞可以提供潜在的治疗机会来抑制PDAC中的细胞侵袭。
Background: Monocytes are a major component of the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC). However, the complex interactions between tumor cells and monocytes and their role in tumor invasion have not been fully established.Methods: To specifically test the impact of interaction on invasive potential two PDAC cell lines PaTu8902 and CFPAC-1 were selected on their ability to form invasive adhesions, otherwise known as invadopodia and invade in a spheroid invasion assay.Results: Interestingly when the PDAC cells were co-cultured with undifferentiated THP1 monocyte-like cells invadopodia formation was significantly suppressed. Moreover, conditioned media of THP1 cells (CM) was also able to suppress invadopodia formation. Further investigation revealed that both tissue inhibitor of metalloproteinase (TIMP) 1 and 2 were present in the CM. However, suppression of invadopodia formation was found that was specific to TIMP2 activity.Conclusions: Our findings indicate that TIMP2 levels in the tumour microenvironment may have prognostic value in patients with PDAC. Furthermore, activation of TIMP2 expressing monocytes in the primary tumour could present a potential therapeutic opportunity to suppress cell invasion in PDAC.